Depression -Maudsley

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

SSRIs are solely responsible for causing sexual dysfunction.

False

TCAs are known to cause hypertension as a side effect.

False

MAOIs can potentially lead to hypertensive crisis when consumed with tyramine-rich foods.

True

Short half-life antidepressants are less likely to cause discontinuation symptoms than those with longer half-lives.

False Signup and view all the answers

Fluvoxamine is a potent inhibitor of CYP2D6 and can affect theophylline serum levels.

False Signup and view all the answers

All antidepressant drugs have the potential to cause drug interactions.

True Signup and view all the answers

Antidepressants are always the first-line treatment for all types of depression.

False Signup and view all the answers

The treatment of moderate to severe depression includes the recommendation of a generic SSRI.

True Signup and view all the answers

Withdrawal from antidepressants should be done suddenly to avoid any negative effects.

False Signup and view all the answers

The use of electroconvulsive therapy (ECT) is only supported in mild cases of depression.

False Signup and view all the answers

Patients should be informed about the potential withdrawal effects when prescribed antidepressants.

True Signup and view all the answers

Psychological treatments can serve as a first-line alternative to antidepressants in severe depression.

False Signup and view all the answers

For treatment-resistant depression, strategies may include the addition of lithium or an antipsychotic.

True Signup and view all the answers

Patients with two prior episodes of depression should receive treatment for a minimum of one year.

False Signup and view all the answers

The new NICE Guidelines for depression treatment are expected to be published in 2021/2022.

True Signup and view all the answers

All antidepressants show a pattern of response where the rate of improvement is highest during weeks 4-6.

False Signup and view all the answers

Approximately 30% of patients with moderate-severe depression will respond to a placebo treatment.

True Signup and view all the answers

Antidepressants are only recommended for patients with severe major depressive disorder.

False Signup and view all the answers

SSRIs are generally considered less tolerable compared to older tricyclic antidepressants (TCAs).

False Signup and view all the answers

Only 9% of comparisons in studies showed antidepressants separate from placebo when using total Hamilton Depression Rating Scale scores.

False Signup and view all the answers

A number needed to treat (NNT) of 5 indicates that for every 5 patients treated with an antidepressant, 1 will benefit compared to those receiving a placebo.

True Signup and view all the answers

Antidepressants typically take effect within the first week of treatment as seen in larger trials.

True Signup and view all the answers

Dual re-uptake inhibitors such as venlafaxine are tolerated better than SSRIs.

False Signup and view all the answers

The use of 'depressed mood' alone as an efficacy measure showed better results in drug comparisons than using total depression scales.

True Signup and view all the answers

A flexible approach is usually required to find the right drug for each patient due to marked inter-individual variation in tolerability.

True Signup and view all the answers

Antidepressants should typically be continued for 6-9 months after a single episode of depression.

True Signup and view all the answers

There is a consensus that long-term treatment with antidepressants is beneficial for all patients.

False Signup and view all the answers

Antidepressants are not effective in treating anxiety spectrum disorders.

False Signup and view all the answers

The majority of patients respond well to the first antidepressant prescribed.

False Signup and view all the answers

Young people have the lowest risk associated with the use of antidepressants.

False Signup and view all the answers

Treatment-emergent suicidal ideation can occur with any antidepressant treatment.

True Signup and view all the answers

There is clear and conclusive evidence regarding the optimal duration of treatment for adjunct regimens.

False Signup and view all the answers

Fluoxetine and paroxetine can both lead to increased health risks due to their effects on CYP2D6.

True Signup and view all the answers

All types of antidepressants have been implicated in increased suicidal thoughts and behaviors in young adults.

True Signup and view all the answers

Switching from one antidepressant to another does not influence the risk of suicidal behaviors in patients aged 75 and over.

False Signup and view all the answers

Electrolyte disturbances from diuretics can reduce the cardiotoxic effects of tricyclic antidepressants (TCAs).

False Signup and view all the answers

Both the initiation and cessation of antidepressants are associated with increased suicide and self-harm rates.

True Signup and view all the answers

Tamoxifen is an example of a pro-drug that may experience treatment failure due to the interactions with certain antidepressants.

True Signup and view all the answers

Antidepressants do not require monitoring for potential drug interactions when switching between them.

False Signup and view all the answers

The cardiotoxicity of TCAs increases when combined with electrolyte-altering medications.

True Signup and view all the answers

What is the recommended daily dose of Sertraline?

50mg/day Signup and view all the answers

The recommended minimum effective dose of Agomelatine is 50mg/day.

False Signup and view all the answers

What is the minimum effective dose of Mirtazapine?

30mg/day Signup and view all the answers

The recommended dose of Fluoxetine is __________ mg/day.

20 Signup and view all the answers

Match the following antidepressants with their respective recommended doses:

Citalopram = 20mg/day Duloxetine = 60mg/day Lofepramine = 140mg/day Venlafaxine = 75mg/day Signup and view all the answers

Which of the following is suggested as the first-choice medication for depression?

Selective serotonin reuptake inhibitors (SSRIs) Signup and view all the answers

Monitoring a patient's response to antidepressant treatment should occur weekly for the first 1-2 weeks.

True Signup and view all the answers

What is the importance of involving the patient in the discussion about drug choice?

To ensure a good therapeutic alliance and improve medication response. Signup and view all the answers

If a patient experiences no effect or poor tolerance from the initial antidepressant, the next step is to switch to a __________ antidepressant.

different Signup and view all the answers

Match the following antidepressants with their alternative options:

Mirtazapine = Sedation required Vortioxetine = Third-choice option Agomelatine = Consider if others fail SSRIs = First choice Signup and view all the answers

What should be assessed after initiating antidepressant treatment?

Treatment efficacy Signup and view all the answers

Antidepressants should be maintained for at least 6-9 months after a single episode of depression.

True Signup and view all the answers

What are the suggested alternative treatment options if initial antidepressants are ineffective?

Mirtazapine, Vortioxetine, Agomelatine. Signup and view all the answers

Patients should be informed about the potential __________ effects when prescribed antidepressants.

withdrawal Signup and view all the answers

How long should a patient be monitored if they have not responded to the increased dose of a new antidepressant?

3-4 weeks Signup and view all the answers

Which of the following is considered the best scale to measure severity and change in depression?

Montgomery–Asberg Depression Rating Scale (MADRS) Signup and view all the answers

SSRI medications are generally not recommended for depression treatment in patients needing sedation.

True Signup and view all the answers

What percentage of patients who do not show improvement at two weeks are likely to eventually respond to treatment?

30% Signup and view all the answers

If a patient cannot tolerate one SSRI, they may still tolerate another ______________.

SSRI Signup and view all the answers

Match the following antidepressants with their respective properties:

Agomelatine = Lowest drop-out rates SSRIs = First choice for most patients Mirtazapine = Used for sedation Dual-action drugs = Most effective in trials Signup and view all the answers

Which option represents a better-supported choice for treatment-resistant depression?

Combining antidepressants Signup and view all the answers

Switching within a drug class is shown to be ineffective for some patients.

False Signup and view all the answers

What are the two neurotransmitters that dual-action drugs primarily affect?

Norepinephrine and serotonin Signup and view all the answers

Which treatment is suggested to be switched after treatment failure?

Vortioxetine Signup and view all the answers

Increasing the dose of SSRIs generally leads to significant improvements in depression.

False Signup and view all the answers

What is a good predictor of overall non-response in antidepressant treatment?

Non-response at 2-6 weeks Signup and view all the answers

Patients should switch treatments if there is no improvement after ______ weeks.

3-4 Signup and view all the answers

Match the following medications with their known characteristics:

Citalopram = First-stage treatment in STAR*D Bupropion = Augmentation option T3 = Augmentation with renewed interest Nortriptyline = Formerly less acknowledged option Signup and view all the answers

Which option reflects common misconceptions regarding treatment-resistant depression?

Non-response is considered abnormal. Signup and view all the answers

The STAR*D program confirmed that treatment-resistant depression requires a rigid approach.

False Signup and view all the answers

What percentage of subjects achieved remission after the first stage of the STAR*D study?

28% Signup and view all the answers

The combination of mirtazapine and venlafaxine was found to be _________ and has a safety profile.

safe Signup and view all the answers

Which outcome is mainly assessed in the STAR*D program?

Remission of symptoms Signup and view all the answers

What is a common side effect of adding aripiprazole to an antidepressant?

Akathisia Signup and view all the answers

Lithium is known to be well tolerated at higher plasma levels.

False Signup and view all the answers

What does combining olanzapine and fluoxetine aim to address in treatment-resistant depression?

Treatment-resistant depression Signup and view all the answers

Adding __________ to an SSRI/SNRI can provide a plausible explanation for an antidepressant effect.

quetiapine Signup and view all the answers

Match the disadvantages of the treatments to their respective treatments:

Add aripiprazole = Insomnia may be problematic Add Lithium = Potentially toxic; needs monitoring Combine olanzapine and fluoxetine = Risk of weight gain Add quetiapine = Dry mouth and sedation can be problematic Signup and view all the answers

Which treatment is not licensed for depression in the UK?

SSRI + Bupropion Signup and view all the answers

Weight gain is not a concern when prescribing mirtazapine.

False Signup and view all the answers

What is the daily dose range for adding aripiprazole to an antidepressant?

2-20 mg/day Signup and view all the answers

Combining SSRIs with __________ is suggested to improve sexual adverse effects.

bupropion Signup and view all the answers

Match the treatment options with their evidence status:

Add aripiprazole = Good evidence base Add Lithium = Well established Add quetiapine = Plausible explanation for efficacy SSRI + Bupropion = Supported by STAR*D Signup and view all the answers

Which of the following is a potential advantage of adding ketamine to the treatment plan for depression?

Immediate improvement in mood Signup and view all the answers

Intranasal esketamine has a dosage range of 28-84mg.

True Signup and view all the answers

What is the usual monitoring required for the addition of tri-iodothyronine in depression treatment?

Clinical and biochemical TFT monitoring Signup and view all the answers

Electroconvulsive therapy (ECT) is usually reserved for __________ treatment.

last-line Signup and view all the answers

Match the treatment options with their corresponding advantages:

Add ketamine = Very rapid response and high remission rate Add lamotrigine = Best tolerated augmentation strategy ECT = Well established and effective Add tri-iodothyronine = Usually well tolerated Signup and view all the answers

What is a disadvantage of using lamotrigine as an adjunct treatment?

Risk of rash Signup and view all the answers

Adding tri-iodothyronine is contraindicated for bipolar depression.

False Signup and view all the answers

Name a potential cognitive effect associated with the use of ketamine in treatment-resistant depression.

Confusion Signup and view all the answers

Electroconvulsive therapy (ECT) necessitates __________.

general anaesthetic Signup and view all the answers

Which antidepressant is probably best tolerated according to the provided treatments?

Lamotrigine Signup and view all the answers

Which of the following treatments for treatment-resistant depression has growing evidence of a prompt and sizeable effect?

Hyoscine (Scopolamine) Signup and view all the answers

Buprenorphine has reasonable evidence supporting its use for treatment-resistant depression despite having contraindications.

True Signup and view all the answers

What is the maximum daily dose of Amantadine suggested for treatment-resistant depression?

300mg Signup and view all the answers

One pilot study showed promising results for __________ at a dose of up to 10mg/day for treatment-resistant depression.

Mecamylamine Signup and view all the answers

Match the following treatments with their comments:

Dexamethasone = Limited data Ayahuasca = Effective but specialist use only Minocycline = Several positive meta-analyses, failed RCT in bipolar depression Oestrogens = Limited data Signup and view all the answers

What is the possible dose-sensitive total dose for Omega-3-triglycerides in antidepressant treatment?

60% Signup and view all the answers

Pramipexole has no published randomized controlled trials supporting its effectiveness.

False Signup and view all the answers

What dosage of Venlafaxine is recommended to be initiated in primary care?

<blockquote> 200mg/day </blockquote> Signup and view all the answers

The treatment with __________ is supported by STAR*D.

SSRI + Buspirone Signup and view all the answers

Match the following treatments with their comments:

Psilocybin = Effective but specialist use only. Zinc = 25mg Zn+/day Testosterone gel = Effective in those with low testosterone levels. S-adenosyl-l-methionine = Use weakly supported by a Cochrane review Signup and view all the answers

Ketamine is classified as a competitive NMDA receptor antagonist.

False Signup and view all the answers

Esketamine is a more potent NMDA receptor binder than R-ketamine.

True Signup and view all the answers

The optimal route for administering ketamine for treatment-resistant depression is fully established.

False Signup and view all the answers

Ketamine's antidepressant effects can be observed within hours after administration.

True Signup and view all the answers

All routes of ketamine administration, including oral and subcutaneous, have equal evidence for efficacy.

False Signup and view all the answers

NMDA receptor blockade on GABAergic interneurons leads to suppressed glutamate release.

False Signup and view all the answers

The esketamine nasal spray has been approved for use in Europe and Canada for treatment-resistant depression.

False Signup and view all the answers

Ketamine's mechanism of action involves the activation of AMPA receptors following an increase in glutamate.

True Signup and view all the answers

Ketamine administered at antidepressant doses can lead to significant dissociative symptoms.

True Signup and view all the answers

Patients can safely drive after receiving a test dose of ketamine.

False Signup and view all the answers

Laryngospasm is a common side effect associated with ketamine administration.

False Signup and view all the answers

Physical monitoring of blood pressure and heart rate is required during and after ketamine administration.

True Signup and view all the answers

Lower doses of ketamine given orally are more likely to induce strong dissociative symptoms.

False Signup and view all the answers

A fixed dosing strategy for ketamine has been universally established across all routes of administration.

False Signup and view all the answers

It is sufficient for any clinician to observe patients during ketamine administration without specific training.

False Signup and view all the answers

Psychotic depression has a better long-term outcome compared to non-psychotic depression.

False Signup and view all the answers

Quetiapine and olanzapine have no antidepressant effects.

False Signup and view all the answers

Withdrawal of olanzapine from sertraline co-therapy can improve outcomes in psychotic depression.

False Signup and view all the answers

The optimum duration of treatment with antidepressants and antipsychotics for psychotic depression is well established.

False Signup and view all the answers

ECT may be more protective against relapse in psychotic depression than non-psychotic depression.

True Signup and view all the answers

Antidepressants are always the first-line treatment for psychotic depression.

False Signup and view all the answers

Patients with psychotic depression are less likely to attempt suicide than those with non-psychotic depression.

False Signup and view all the answers

A combination of antidepressant and antipsychotic medications is always ineffective.

False Signup and view all the answers

Mifepristone is not associated with rapid effects in the treatment of psychotic depression.

False Signup and view all the answers

The use of ketamine has shown no effectiveness in psychotic depression.

False Signup and view all the answers

Patients with psychotic symptoms are generally less severely unwell than those without psychotic symptoms.

False Signup and view all the answers

Psychotic depression has a lifetime risk of up to 5%.

False Signup and view all the answers

Combined treatment with both an antidepressant and an antipsychotic is often recommended for psychotic depression.

True Signup and view all the answers

TCAs are less effective than newer antidepressants in treating psychotic depression.

False Signup and view all the answers

A combination of olanzapine and fluoxetine showed a response rate of 64% in one large RCT.

True Signup and view all the answers

Studies indicate that treatment with olanzapine alone results in better remission rates than with olanzapine plus sertraline.

False Signup and view all the answers

Venlafaxine plus quetiapine is more effective than venlafaxine alone and imipramine alone.

False Signup and view all the answers

A review of all combination studies concluded that an antipsychotic combined with an antidepressant shows no advantages.

False Signup and view all the answers

NICE recommends against augmenting an antidepressant with an antipsychotic in the treatment of acute psychotic depression.

False Signup and view all the answers

There are many studies of newer antidepressants and atypical antipsychotics specifically for psychotic depression.

False Signup and view all the answers

What is the preferred method when switching antidepressants?

Cross-tapering Signup and view all the answers

Abruptly switching from one SSRI to another is always advised due to their similar effects.

False Signup and view all the answers

What is one potential risk of co-administering two antidepressants?

Serotonin syndrome Signup and view all the answers

When switching to a drug with a similar mode of action, abrupt cessation may be __________.

acceptable Signup and view all the answers

Match the following antidepressants with their characteristics:

Agomelatine = Melatonin agonist and 5HT2C antagonist Fluoxetine = SSRI often used for abrupt switch Venlafaxine = Dual re-uptake inhibitor Paroxetine = SSRI with risk of drug interactions Signup and view all the answers

Which factor should be considered when determining the switching strategy between antidepressants?

Pharmacokinetic properties Signup and view all the answers

Extended withdrawal periods may be necessary to prevent discontinuation symptoms.

True Signup and view all the answers

What is one potential danger of simultaneously administering two antidepressants?

Hypotension Signup and view all the answers

The speed of cross-tapering should be guided by patient __________.

tolerability Signup and view all the answers

Which of these antidepressants is associated with lower risks of discontinuation syndrome?

Agomelatine Signup and view all the answers

Which symptoms are associated with mild serotonin syndrome?

Insomnia, anxiety, nausea Signup and view all the answers

Moderate serotonin syndrome includes symptoms like hyper-reflexia and tachycardia.

False Signup and view all the answers

Name one symptom of moderate serotonin syndrome.

Agitation Signup and view all the answers

Symptoms of mild serotonin syndrome can include and .

nausea, anxiety Signup and view all the answers

Match the severity level to the corresponding symptoms of serotonin syndrome:

Mild = Insomnia, anxiety, nausea, diarrhea Moderate = Agitation, myoclonus, tremor Severe = Hyperthermia, muscle rigidity, altered mental status Critical = Severe autonomic instability, confusion Signup and view all the answers

What is the primary difference between 'discontinuation symptoms' and 'withdrawal symptoms'?

Withdrawal symptoms indicate addiction Signup and view all the answers

Antidepressants can cause cravings similar to addictive substances.

False Signup and view all the answers

What distinguishes withdrawal symptoms from a relapse of the original disorder?

Rapid onset and response to reintroduction of the antidepressant. Signup and view all the answers

Withdrawal symptoms such as brain zaps and dizziness are often associated with __________ and related drugs.

SSRIs Signup and view all the answers

Match the following symptoms with their corresponding category:

Diarrhea = Somatic Symptoms Brain zaps = Psychological Symptoms Nausea = Somatic Symptoms Dizziness = Somatic Symptoms Signup and view all the answers

Which category does 'dizziness' fall under in SSRI withdrawal symptoms?

Disequilibrium Signup and view all the answers

Genital hypersensitivity is categorized under gastrointestinal symptoms.

False Signup and view all the answers

Name one cognitive symptom associated with SSRI withdrawal syndrome.

Confusion Signup and view all the answers

Symptoms such as nausea and vomiting fall under __________ symptoms.

Gastrointestinal Signup and view all the answers

Match the following withdrawal symptoms to their respective categories:

Irritability = Affective symptoms Palinopsia = Sensory symptoms Insomnia = Sleep disturbance Tremor = General somatic symptoms Signup and view all the answers

Which of the following is NOT a sensor symptom of SSRI withdrawal?

Nightmares Signup and view all the answers

Tachycardia is a common general somatic symptom associated with SSRI withdrawal syndrome.

True Signup and view all the answers

List two affective symptoms that can occur during SSRI withdrawal.

Anxiety/agitation, Low mood/depression Signup and view all the answers

Which pharmacological factor is correlated with the severity and onset of antidepressant withdrawal symptoms?

Drug half-lives Signup and view all the answers

Higher receptor affinities always lead to fewer withdrawal symptoms.

False Signup and view all the answers

Name one treatment factor that influences antidepressant withdrawal symptoms.

Duration of treatment, Dose, or Method of tapering. Signup and view all the answers

Patients with a history of __________ experience anticipation effects that can impact withdrawal symptoms.

prior treatment Signup and view all the answers

Match the following factors with their respective categories:

Venlafaxine = Short half-life antidepressant Paroxetine = Short half-life antidepressant Long-term treatment = Patient-Specific Factor Dose adjustment = Treatment Factor Signup and view all the answers

Antidepressant discontinuation symptoms have a variable incidence, with rates ranging from 9% to 77% for fluoxetine.

True Signup and view all the answers

Symptoms from short half-life antidepressants like venlafaxine can appear within a week of discontinuation.

False Signup and view all the answers

Agomelatine is one of the few antidepressants that does not produce withdrawal symptoms.

True Signup and view all the answers

The Discontinuation–Emergent Signs and Symptoms (DESS) scale is used to measure the intensity of withdrawal symptoms.

True Signup and view all the answers

Antidepressants with shorter half-lives are more likely to produce withdrawal symptoms than those with longer half-lives.

True Signup and view all the answers

Which symptom is commonly associated with MAOIs?

Vivid dreams Signup and view all the answers

Bupropion is known to commonly cause panic attacks.

False Signup and view all the answers

Name one common side effect of NaSSAs like mirtazapine.

Anxiety Signup and view all the answers

Agomelatine is associated with a very low risk of __________ symptoms.

discontinuation Signup and view all the answers

Match the following antidepressants with their associated symptoms:

Agomelatine = Anxiety, headache, insomnia Trazodone = Hypomania, depersonalization Somatic Distress = General GI distress MAOIs = Hallucinations, cognitive impairment Signup and view all the answers

Which of the following symptoms have been reported with TCAs?

Cardiac arrhythmia Signup and view all the answers

Serotonin modulators like vortioxetine have no reported symptoms.

True Signup and view all the answers

What is a symptom occasionally reported with MAOIs?

Hallucinations Signup and view all the answers

The symptom of __________ is described in case reports for both Agomelatine and Bupropion.

irritability Signup and view all the answers

Withdrawal symptoms from antidepressants can be confused with a relapse of illness.

True Signup and view all the answers

Short half-life antidepressants are associated with a lower risk of withdrawal symptoms compared to long half-life antidepressants.

False Signup and view all the answers

Many individuals experience withdrawal symptoms even with gradual tapering of antidepressants.

True Signup and view all the answers

Antidepressants are universally considered addictive by medical standards.

False Signup and view all the answers

Children and adolescents are less likely to experience withdrawal symptoms from antidepressant discontinuation.

False Signup and view all the answers

Switching to an antidepressant with a shorter half-life decreases the likelihood of discontinuation symptoms.

False Signup and view all the answers

Gradually tapering off antidepressants can help prevent severe withdrawal symptoms.

True Signup and view all the answers

Fluoxetine is associated with a lower incidence of withdrawal symptoms than other similar antidepressants.

True Signup and view all the answers

Those who have experienced withdrawal symptoms before have a lower risk of experiencing them again.

False Signup and view all the answers

Emergent suicidal thoughts can occur upon discontinuation of antidepressants like paroxetine.

True Signup and view all the answers

Patients should be informed that abrupt cessation of antidepressants is likely to result in fewer withdrawal symptoms.

False Signup and view all the answers

Anticholinergic agents may be beneficial in managing withdrawal symptoms from tricyclic antidepressants.

True Signup and view all the answers

Patients receiving MAOIs may require a longer tapering period to prevent withdrawal symptoms.

True Signup and view all the answers

Abrupt discontinuation of antidepressants is always safe and does not lead to negative outcomes.

False Signup and view all the answers

Discontinuation symptoms can appear after simply missing a dose of an antidepressant with a short half-life.

True Signup and view all the answers

The majority of patients prescribed antidepressants adhere to their treatment without skipping doses.

False Signup and view all the answers

Reintroducing the original antidepressant is advised only if symptoms are mild.

False Signup and view all the answers

Patients often incorrectly assume that antidepressants are not associated with withdrawal symptoms.

True Signup and view all the answers

Patients taking higher doses of antidepressants have an increased risk of withdrawal symptoms.

True Signup and view all the answers

Psychological treatment is always preferred over antidepressants for managing major depression.

False Signup and view all the answers

What type of curve does panel (a) illustrate in relation to Sertraline dose and receptor effect?

Sigmoid curve Signup and view all the answers

The reduction in dose of Sertraline resulted in a hyperbolic response according to panel (b).

False Signup and view all the answers

What kind of dose reduction is shown in panel (b) regarding Sertraline?

Hyperbolic dose reduction Signup and view all the answers

Panel (a) demonstrates that smaller reductions in Sertraline dose lead to _________ withdrawal effects.

more pronounced Signup and view all the answers

Match the following characteristics with their corresponding panels:

Panel (a) = Greater effect reduction with smaller dose reductions Panel (b) = Dependence on dose response Signup and view all the answers

Withdrawal symptoms should be monitored for a duration of 2–4 weeks for all patients.

True Signup and view all the answers

If withdrawal symptoms are severe, the tapering process should continue at the same rate as previously established.

False Signup and view all the answers

It is recommended to reduce fluoxetine dose by decreasing the frequency of dosing.

True Signup and view all the answers

Electroconvulsive therapy (ECT) is not advised to be used concurrently with antidepressants.

False Signup and view all the answers

When tapering antidepressants, the final dose may need to be much less than 1mg to avoid significant effects.

True Signup and view all the answers

Ketamine as an anesthetic improves overall outcomes in ECT treatments.

False Signup and view all the answers

Patients often find it manageable to reduce their antidepressant dosage by more than 10% of the last dose each month.

False Signup and view all the answers

Patients should be told that tapering off antidepressants can cause withdrawal symptoms as severe as taking the medication itself.

False Signup and view all the answers

Mindfulness-based cognitive therapy (MB-CT) has no evidence supporting its use in the process of stopping antidepressants.

False Signup and view all the answers

It is generally difficult to predict how long an individual will need to taper off antidepressants.

True Signup and view all the answers

Patients with a history of withdrawal symptoms should undergo a test reduction of 20-25% when tapering antidepressants.

False Signup and view all the answers

Support during the tapering process is generally not necessary for most patients.

False Signup and view all the answers

Tapering antidepressants too quickly may lead to withdrawal symptoms being misdiagnosed as relapse.

True Signup and view all the answers

When tapering off antidepressants, patients should not be informed of their past experiences as it can lead to anxiety.

False Signup and view all the answers

The most common approach for patients tapering off antidepressants is to stop all medication at once.

False Signup and view all the answers

Withdrawal symptoms from antidepressants should only be monitored for 1 week.

False Signup and view all the answers

Fluoxetine can lead to withdrawal symptoms that are delayed by weeks due to its long half-life.

True Signup and view all the answers

All patients can taper their antidepressant dose by 10% each month without issues.

False Signup and view all the answers

Electroconvulsive therapy (ECT) can cause increased confusion and, in rare cases, delirium.

True Signup and view all the answers

Patients should use liquid formulations of antidepressants when tapering to allow for pharmacologically informed regimens.

True Signup and view all the answers

Tapering antidepressants is generally safely done through sudden cessation of the medication.

False Signup and view all the answers

Sertraline can require a final dose significantly lower than 1mg when tapering.

True Signup and view all the answers

Patients should be aware that the abrupt cessation of antidepressants is the safest method to stop the medication.

False Signup and view all the answers

Most long-standing patients may take around 3 months to taper off antidepressant medication.

True Signup and view all the answers

Mindfulness-based cognitive therapy (MB-CT) has no evidence supporting its help in the process of stopping antidepressants.

False Signup and view all the answers

A test reduction of 5-10% is recommended for patients who are classified as high-risk during tapering.

False Signup and view all the answers

Patients should be reassured that negative symptoms during withdrawal may indicate the need for a lower taper rate instead of a full dose.

True Signup and view all the answers

Involving patients in discussions about their tapering process can alleviate unnecessary anxiety about withdrawal symptoms.

True Signup and view all the answers

Prior negative experiences with tapering should be disregarded as they do not impact the current tapering process.

False Signup and view all the answers

Patients who have had withdrawal symptoms in the past are classified as low-risk when tapering off antidepressants.

False Signup and view all the answers

Benzodiazepines are recommended for use during ECT as they may enhance seizure duration.

False Signup and view all the answers

The effect of SSRIs on seizure duration during ECT is considered minimal, with a small possibility of increased duration.

True Signup and view all the answers

High doses of Venlafaxine can increase the risk of seizure duration during ECT.

False Signup and view all the answers

Mirtazapine may complicate the ECT procedure but is generally considered safe.

False Signup and view all the answers

The use of MAOIs during ECT has no documented effects on seizure duration.

True Signup and view all the answers

Tricyclic antidepressants (TCAs) are known to lower seizure thresholds, making them more advisable during ECT.

False Signup and view all the answers

Duloxetine should always be avoided during ECT due to its potential to complicate the procedure.

False Signup and view all the answers

The use of benzodiazepines is ideal for sedation before ECT due to their short half-life and rapid action.

False Signup and view all the answers

Among psychotropic drugs, only SSRIs are deemed completely safe for use during ECT.

False Signup and view all the answers

Electroconvulsive therapy (ECT) is primarily effective in patients who are on a regimen of SSRIs for their psychiatric conditions.

False Signup and view all the answers

Lithium may potentially increase seizure duration during ECT treatments.

True Signup and view all the answers

Barbiturates are known to increase seizure duration in ECT.

False Signup and view all the answers

Antipsychotic medications like clozapine can safely be used during ECT.

True Signup and view all the answers

Valproate is associated with normalization of seizure thresholds when used in patients undergoing ECT.

True Signup and view all the answers

Clozapine is likely to prolong seizures, and its withdrawal before ECT is often suggested.

True Signup and view all the answers

Using antiseizure medications during ECT is always discouraged.

False Signup and view all the answers

Concomitant use of thiopentone or propofol with lithium treatment is beneficial as it raises seizure thresholds.

False Signup and view all the answers

Antipsychotics like aripiprazole, quetiapine, and ziprasidone have not shown distinct adverse effects during ECT.

True Signup and view all the answers

All types of barbiturates increase the risk of cardiac arrhythmia during ECT.

False Signup and view all the answers

Antiseizure medications are necessary to reduce risks associated with ECT when used as a mood stabilizer.

True Signup and view all the answers

Amfetamines are frequently used in the treatment of depression due to their safety profile.

False Signup and view all the answers

Modafinil is known to induce tolerance and dependence similar to amfetamines.

False Signup and view all the answers

The mood-elevating effects of psychostimulants are typically seen within days after administration.

False Signup and view all the answers

Methylphenidate is more widely utilized in depression treatment than modafinil.

True Signup and view all the answers

Psychostimulants can provide immediate relief in severe, prolonged depression unresponsive to standard treatments.

True Signup and view all the answers

The safety of long-term use of psychostimulants in depression has been well established.

False Signup and view all the answers

Armodafinil is the shorter acting isomer of modafinil.

False Signup and view all the answers

Data about the use of stimulants in depression is comprehensive and conclusive.

False Signup and view all the answers

Monotherapy with Modafinil is proven to be effective for uncomplicated depression.

False Signup and view all the answers

The combined use of SSRI and methylphenidate has a clear effect on improving response time in patients.

False Signup and view all the answers

Dexamphetamine is recommended for use as a monotherapy in cases of uncomplicated depression.

False Signup and view all the answers

Using SSRI with modafinil can lead to improved treatment responses compared to using SSRI alone.

True Signup and view all the answers

The standard recommendation for treating uncomplicated depression prioritizes monotherapy with psychostimulants.

False Signup and view all the answers

Lisdexamfetamine shows superiority over placebo in the treatment of depression when used with an SSRI or SNRI.

False Signup and view all the answers

Tricyclic antidepressants combined with methylphenidate suggest a faster response based on an open-label trial.

True Signup and view all the answers

The overall preference for treating clinically significant depression advocates for the use of psychostimulants.

False Signup and view all the answers

Methylphenidate is considered to have minimal efficacy when used alone for depression.

True Signup and view all the answers

Modafinil is generally not recommended as an adjunctive therapy in the treatment of depression.

False Signup and view all the answers

What is the effect of modafinil when used as an adjunctive treatment for depression with hypersomnia?

Beneficial only for hypersomnia. Signup and view all the answers

SSRIs combined with methylphenidate show no observable benefits for fatigue.

False Signup and view all the answers

What is one treatment option for bipolar depression when other standard treatments fail?

Mood stabilizer and/or antidepressants + modafinil 100-200mg/day Signup and view all the answers

The combination of MAOI and ______ may be a treatment option in refractory illness.

dexamfetamine Signup and view all the answers

Match the following adjunctive treatments for depression with their effects:

SSRI + modafinil 200mg/day = Beneficial effect only on hypersomnia Mood stabilizer + armodafinil 150-200mg/day = Superior to placebo on some measures Methylphenidate or dexamfetamine + antidepressant = Benefit in majority based on large case series Lisdexamfetamine 20-70mg/day + antidepressant = Small, non-significant effect on depressive symptoms compared to placebo Signup and view all the answers

What was the conclusion regarding the combination of mood stabilizer and methylphenidate for bipolar depression?

Results are mixed, with mainly positive outcomes. Signup and view all the answers

The evidence for combining SSRI with modafinil at high doses is strong and well-supported.

False Signup and view all the answers

SSRI combined with ______ showed a clear effect on fatigue in hospice patients.

methylphenidate Signup and view all the answers

Name one adverse effect associated with the use of modafinil.

Suicidal ideation Signup and view all the answers

Match the evaluations with their recommendations for adjunctive treatments:

SSRI + modafinil 200mg/day = Weak evidence base for fatigue Mood stabilizer and/or antidepressants + modafinil = Significantly superior to placebo Methylphenidate or dexamfetamine + antidepressant = Benefit for majority Lisdexamfetamine + antidepressants = Small, non-significant effect Signup and view all the answers

What is one of the benefits observed from the use of Methylphenidate in late-stage terminal cancer?

Decreased fatigue Signup and view all the answers

Dexamfetamine is recommended as a first-line treatment in depression secondary to medical illness.

False Signup and view all the answers

What is the recommended use of Dexamfetamine in the treatment of depression associated with HIV?

As a possible treatment option where fatigue is not responsive to standard antidepressants. Signup and view all the answers

Patients with post-stroke depression should primarily receive ____________ as standard treatment.

standard antidepressants Signup and view all the answers

Match the following conditions with their respective recommended treatment:

Post-stroke depression = Standard antidepressants Late-stage terminal cancer = Methylphenidate and Dexamfetamine HIV-related depression = Dexamfetamine Depression in traumatic brain injury = Methylphenidate Signup and view all the answers

In the treatment of depression in the elderly, what is noted about the combination of Methylphenidate and citalopram?

Rapid effect on mood Signup and view all the answers

Methylphenidate has been shown to improve depressive symptoms, daytime sleepiness, and cognitive function.

True Signup and view all the answers

What is the recommended dosage of Methylphenidate for patients in late-stage terminal cancer?

5-30mg/day Signup and view all the answers

Combination therapy with Methylphenidate and citalopram is recommended only when patients fail to tolerate ____________.

standard antidepressants Signup and view all the answers

What is a significant concern when using Methylphenidate for treating depression in the elderly?

Increased heart rate Signup and view all the answers

Post-stroke depression is seen in at least 30-40% of stroke survivors.

True Signup and view all the answers

Antidepressants may impede cognitive function and slow motor recovery in post-stroke patients.

False Signup and view all the answers

Mirtazapine is suggested as an effective treatment for post-stroke depression.

True Signup and view all the answers

Reboxetine is known to affect platelet activity.

False Signup and view all the answers

Vortioxetine demonstrates significant adverse effects on cardiovascular parameters.

False Signup and view all the answers

Routine use of antidepressants for the prevention of post-stroke depression is strongly recommended.

False Signup and view all the answers

Fluoxetine has been shown to significantly decrease the incidence of all levels of depressive symptoms post-stroke.

False Signup and view all the answers

SSRIs have been conclusively shown to increase the risk of stroke.

False Signup and view all the answers

The use of SSRIs and nortriptyline is widely recommended for post-stroke depression treatment.

True Signup and view all the answers

Nortriptyline is an alternative antidepressant that increases the risk of bleeding.

False Signup and view all the answers

Mirtazapine was ranked first for response rate in a recent meta-analysis of trials.

True Signup and view all the answers

Escitalopram's risks, such as bone fractures and falls, outweigh its benefits in post-stroke depression.

True Signup and view all the answers

Nortriptyline and fluoxetine are considered to have poor safety profiles in the treatment of post-stroke depression.

False Signup and view all the answers

The evidence for SSRIs protecting against embolic stroke is considered strong.

False Signup and view all the answers

Citalopram and escitalopram may be preferred in patients taking warfarin.

True Signup and view all the answers

Antidepressants can be administered via an intra-gastric route when patients have feeding tubes.

True Signup and view all the answers

All formulations of antidepressants are readily available and licensed in the UK.

False Signup and view all the answers

Intra-jejunal tube administration of antidepressants requires special care due to absorption changes.

True Signup and view all the answers

Non-oral administration of antidepressants is advised to be done casually to avoid complications.

False Signup and view all the answers

Some psychotropics not labeled as antidepressants can have pharmacological antidepressant activity.

True Signup and view all the answers

Plasma level monitoring is not useful in assessing the absorption of antidepressants.

False Signup and view all the answers

All prescribers are held accountable for adverse effects when using medications without a license.

True Signup and view all the answers

Nortriptyline hydrochloride has been successfully formulated as a transdermal patch for depression.

False Signup and view all the answers

Oral selegiline may require a tyramine-restricted diet when administered at doses greater than 20mg/day.

True Signup and view all the answers

Transdermal selegiline patches eliminate the need for tyramine restriction altogether.

False Signup and view all the answers

Esketamine has been licensed for treatment-resistant depression in the United Kingdom since 2020.

False Signup and view all the answers

Doxepin capsules can be administered via the rectal route without a special formulation.

True Signup and view all the answers

Sublingual administration of fluoxetine has shown effectiveness in medically compromised patients without any evidence supporting its dose safety.

False Signup and view all the answers

Selegiline in low doses (1.25mg) selectively inhibits MAO-A in the central nervous system and is effective as an antidepressant.

False Signup and view all the answers

Commercially available buccal-adhesive products for doxepin are currently on the market.

False Signup and view all the answers

IV administration of antidepressants is less tolerable than oral administration and can lead to a greater response.

False Signup and view all the answers

Allopregnanolone, marketed as brexanolone, can be used for the treatment of various types of depression.

False Signup and view all the answers

The intravenous preparation of citalopram is associated with a higher risk of QTc prolongation compared to other SSRIs.

True Signup and view all the answers

IV ketamine is known for producing long-lasting antidepressant effects in patients.

False Signup and view all the answers

Transdermal amitriptyline gel has established published data on the plasma levels attained via this route.

False Signup and view all the answers

In patients with unipolar depression, intravenous scopolamine has been shown to provide rapid antidepressant effects.

True Signup and view all the answers

Mirtazapine is available in an intravenous formulation specifically for treating chronic pain conditions.

False Signup and view all the answers

Stopping antidepressant therapy immediately after recovery increases the risk of depressive symptoms returning.

True Signup and view all the answers

Continuing treatment with antidepressants has no effect on the odds of depressive relapse.

False Signup and view all the answers

About half of those who experience a first-onset episode of major depressive disorder recover and have no further episodes.

True Signup and view all the answers

People with depression have a lower risk of cardiovascular disease compared to the general population.

False Signup and view all the answers

Withdrawal from antidepressants should only be attempted if a patient has been free from significant symptoms for 6–8 weeks.

False Signup and view all the answers

Long episode duration is a factor that can increase the risk of recurrence in major depressive disorder.

True Signup and view all the answers

Major depressive disorder is recurrent in approximately 50% of cases.

False Signup and view all the answers

Discontinuation of successful antidepressant therapy after 12 weeks is the recommended guideline to minimize relapse.

False Signup and view all the answers

The absolute risk of relapse decreases with prolonged usage of antidepressants beyond three years.

True Signup and view all the answers

Non-continuous use of antidepressants during the first 6 months of treatment predicts lower rates of relapse.

False Signup and view all the answers

Antidepressant treatment should always be continued for a minimum of two years for all patients.

False Signup and view all the answers

The efficacy of lithium as the sole prophylactic drug in unipolar depression is well established.

False Signup and view all the answers

Withdrawal from antidepressants should be done gradually under specialist supervision to minimize risks.

True Signup and view all the answers

Studies indicate that response to antidepressants diminishes with the number of previously prescribed antidepressants.

True Signup and view all the answers

Maintenance treatment with antidepressants has been proven to be beneficial only in elderly patients.

False Signup and view all the answers

Patients who experience residual symptoms after depression treatment have a higher risk of relapse.

True Signup and view all the answers

A minority of views suggest that antidepressants can worsen the conditions they are meant to treat.

True Signup and view all the answers

Antidepressants are known to cause new long-term side effects when used for the treatment of depression.

False Signup and view all the answers

Lower doses of antidepressants are recommended for young adults and adolescents as a standard practice.

False Signup and view all the answers

Antidepressant prophylaxis is typically required with the same drug that succeeded in the initial treatment.

False Signup and view all the answers

Pharmacokinetic interactions occur when one drug alters the absorption, distribution, metabolism, or elimination of another drug.

True Signup and view all the answers

Fluvoxamine is a potent inducer of CYP2D6, which has less clinical significance than its inhibition.

False Signup and view all the answers

Pharmacodynamic interactions can occur through mechanisms like competition at receptor sites or alteration of neurotransmitter pathways.

True Signup and view all the answers

The use of anticholinergic drugs such as antihistamines can potentially exacerbate cognitive impairment.

True Signup and view all the answers

The risk of GI bleeds is decreased when SSRIs are combined with NSAIDs.

False Signup and view all the answers

Alpha-1 blockers are known for increasing blood pressure when combined with sympathomimetic drugs.

False Signup and view all the answers

Tricyclic antidepressants have no sedative effects and are not associated with the use of alcohol.

False Signup and view all the answers

SSRIs can potentially increase the risk of bleeding when combined with NSAIDs.

True Signup and view all the answers

Up to 1 extra woman in 20 may die within 5 years when taking paroxetine with tamoxifen due to potential drug interactions.

True Signup and view all the answers

MAOIs are effective in preventing the breakdown of serotonin, catecholamines, and dietary tyramine.

True Signup and view all the answers

Antidepressant drug interactions are fully predictable and do not vary by patient-specific factors.

False Signup and view all the answers

The combination of serotonergic drugs can lead to serotonin syndrome, a possibly fatal condition.

True Signup and view all the answers

Antidepressants with shorter half-lives are more likely to lead to withdrawal symptoms compared to those with longer half-lives.

False Signup and view all the answers

The pharmacokinetic properties of a drug can influence the outcome of drug interactions.

True Signup and view all the answers

Caution is especially important when combining drugs that lower the seizure threshold, like antipsychotics, with patients treated for epilepsy.

True Signup and view all the answers

Which CYP enzyme is inhibited by Chlorpromazine?

CYP2D6 Signup and view all the answers

Rifampicin is an inhibitor of CYP2C19.

False Signup and view all the answers

Name one inducer of CYP3A4/5/7.

Carbamazepine Signup and view all the answers

The CYP enzyme with a genetic polymorphism affecting about 20% of Asians is __________.

CYP2C19 Signup and view all the answers

Match the following CYP enzymes with their respective inducers:

CYP1A2 = Carbamazepine CYP2B6 = Ritonavir CYP2C9 = Phenytoin CYP2D6 = Rifampicin Signup and view all the answers

Which drug is a potent inhibitor of CYP1A2?

Ciprofloxacin Signup and view all the answers

Grapefruit juice is an inducer of CYP3A4/5/7.

False Signup and view all the answers

Identify one substrate that is metabolized by CYP2C19.

Omeprazole Signup and view all the answers

The percentage of poor metabolisers for CYP2B6 is estimated to be __________.

2-10% Signup and view all the answers

Which of the following combinations includes a drug that can induce both CYP2C9 and CYP3A4/5/7?

Carbamazepine, Prednisolone Signup and view all the answers

Which antidepressant is associated with a small decrease in mean heart rate?

Fluoxetine Signup and view all the answers

Citalopram has no effect on QTc interval.

False Signup and view all the answers

What effect does Bupropion have on blood pressure?

Slight increases in blood pressure Signup and view all the answers

Duloxetine is not recommended in patients with __________ disease.

cardiac Signup and view all the answers

Match the following antidepressants with their effects on QTc:

Agomelatine = Single case of QTc prolongation Bupropion = QTc shortening Citalopram = Dose-related increase in QTc Duloxetine = Isolated reports of QTc prolongation Signup and view all the answers

Which antidepressant has no specific contraindication after myocardial infarction (MI)?

Agomelatine Signup and view all the answers

What arrhythmia has been reported with Citalopram overdose?

Torsade de Pointes Signup and view all the answers

Fluvoxamine is associated with significant changes in ECG.

False Signup and view all the answers

The recommended care for patients taking __________ is to monitor their blood pressure due to interaction potential.

Bupropion Signup and view all the answers

Which drug is cautiously recommended for use in patients without specific contraindications?

Agomelatine Signup and view all the answers

Which drug is contraindicated in patients with a recent myocardial infarction?

Lofepramine Signup and view all the answers

MAOIs have no effect on heart rate.

False Signup and view all the answers

What effect does Milnacipran have on heart rate?

Slight increase (approximately 10 bpm) Signup and view all the answers

Mirtazapine is considered a good alternative to ________ due to its safety profile post-MI.

SSRIs Signup and view all the answers

Match each drug with its effect on blood pressure:

Levomilnacipran = Small increase Paroxetine = Minimal effect Reboxetine = Marginal increase MAOIs = Postural hypotension Signup and view all the answers

Which drug is indicated for caution in patients with cardiac diseases?

All of the above Signup and view all the answers

Paroxetine is considered unsafe for use post-myocardial infarction.

False Signup and view all the answers

What is the effect of Reboxetine on heart rate?

Significant increase Signup and view all the answers

Moclobemide has a marginal decrease in heart rate and a ________ effect on blood pressure.

minimal Signup and view all the answers

Which drug is associated with the risk of arrhythmias particularly at higher doses?

Lofepramine Signup and view all the answers

What effect does Sertraline have on heart rate?

Minimal effect on heart rate Signup and view all the answers

Sertraline has no effect on QTc interval at standard doses.

True Signup and view all the answers

Name one potential electrical disturbance that can result from antidepressants.

Arrhythmia Signup and view all the answers

The effect of Sertraline on blood pressure is __________.

Minimal Signup and view all the answers

Match the drug to its effect on heart rate:

Sertraline = Minimal effect Venlafaxine = Increases heart rate significantly Mirtazapine = Minimal effect TCAs = Risk of arrhythmias Signup and view all the answers

What is one of the potential risks associated with the use of SSRIs in patients with cardiac disease?

Anti-platelet activity Signup and view all the answers

SSRIs and mirtazapine have shown a beneficial effect on mortality after a myocardial infarction.

True Signup and view all the answers

Name a suggested alternative to SSRIs for treating depression in patients with cardiac disease.

Mirtazapine Signup and view all the answers

Untreated depression worsens prognosis in __________ disease.

cardiovascular Signup and view all the answers

Match the following antidepressants with their associated effects or considerations:

SSRIs = May reduce arrhythmia frequency and have anti-platelet activity Mirtazapine = Suggested alternative with bleeding disorder risks CBT = May be ineffective post-myocardial infarction Antidepressants in general = Beneficial in treating post-MI depression Signup and view all the answers

CBT is considered an effective treatment for depression following a myocardial infarction.

False Signup and view all the answers

Tricyclic antidepressants (TCAs) can cause PR, QRS, and QT prolongation.

True Signup and view all the answers

Lofepramine is associated with a high risk of overdose arrhythmogenicity similar to other TCAs.

False Signup and view all the answers

Venlafaxine has established evidence supporting its role as a strong sodium channel antagonist.

False Signup and view all the answers

Antidepressants have no association with sudden cardiac death during clinical use.

False Signup and view all the answers

SSRIs are linked to QT changes when used at normal clinical doses.

True Signup and view all the answers

Desvenlafaxine is known to prolong the QT interval even in overdose.

False Signup and view all the answers

Clinical monitoring of ECG is less meaningful than plasma level monitoring for patients taking tricyclic antidepressants.

False Signup and view all the answers

Sertraline can increase the QT interval by 5–10ms at a dosage of 400mg per day.

True Signup and view all the answers

ECG changes associated with massive overdose of antidepressants are very common.

False Signup and view all the answers

Normal clinical doses of most SSRIs do not show QT changes.

True Signup and view all the answers

Higher doses of citalopram (>40mg) were associated with more adverse outcomes than lower doses.

False Signup and view all the answers

Vortioxetine has an effect on QT intervals.

False Signup and view all the answers

Sertraline is recommended for patients who have had a recent myocardial infarction.

True Signup and view all the answers

All marketed antidepressants have been linked to arrhythmia.

True Signup and view all the answers

Escitalopram has been shown to affect mortality in patients with heart failure.

False Signup and view all the answers

Citalopram and escitalopram have very low overdose toxicity despite QT prolongation.

True Signup and view all the answers

Tricyclic antidepressants (TCAs) are generally safe for patients at risk of serious arrhythmia.

False Signup and view all the answers

SSRIs are associated with an increased risk of arrhythmia in older people.

True Signup and view all the answers

The arrhythmogenic potential of antidepressants is not influenced by dosage.

False Signup and view all the answers

Monitoring of patients prescribed antidepressants is unnecessary if they have no prior cardiac issues.

False Signup and view all the answers

Which class of antidepressants has the highest risk of hyponatremia according to the evidence provided?

SSRIs Signup and view all the answers

SNRIs have a low risk of hyponatremia based on strong evidence.

False Signup and view all the answers

What is the risk of hyponatremia for Bupropion?

Low Signup and view all the answers

The risk of hyponatremia associated with __________ antidepressants is categorized as moderate.

Tricyclics Signup and view all the answers

Match each antidepressant to its corresponding risk level of hyponatremia:

SSRIs = High NaSSas = Low Bupropion = Low MAOIs = Low Signup and view all the answers

Hyponatraemia can manifest with symptoms such as dizziness, nausea, and seizures.

True Signup and view all the answers

The risk of drug-induced hyponatraemia increases significantly after 6 months of starting antidepressants.

False Signup and view all the answers

Older age is considered a significant risk factor for developing hyponatraemia while on antidepressants.

True Signup and view all the answers

Reducing fluid intake could help manage mild cases of hyponatraemia.

True Signup and view all the answers

Serum sodium levels lower than 136 mmol/L are considered within the normal range.

False Signup and view all the answers

What is the usual nature of prolactin rises when caused by antidepressant use?

Small and short-lived Signup and view all the answers

Routine monitoring of prolactin levels is recommended for all patients on antidepressants.

False Signup and view all the answers

What should be done if symptomatic hyperprolactinaemia is confirmed in a patient on antidepressants?

Switch to mirtazapine or an alternative SSRI. Signup and view all the answers

The indirect modulation of prolactin release is influenced by serotonin through 5HT1C and 5HT2 receptors, primarily controlled by __________.

dopamine Signup and view all the answers

Match the following medications to their outcomes when dealing with hyperprolactinaemia from antidepressants:

Mirtazapine = Recommended switch option Alternative SSRI = Potential resolution of symptoms Fluoxetine = No effect on breast cancer risk Routine monitoring = Not recommended Signup and view all the answers

Which antidepressant has a clear association with prolactin elevation based on case reports?

SNRIs Signup and view all the answers

Mirtazapine has strong evidence showing it affects prolactin levels.

False Signup and view all the answers

What unusual side effects have been reported with the use of SNRIs?

Galactorrhea Signup and view all the answers

The drug group known for very occasional reports of increased prolactin includes __________.

MAOIs Signup and view all the answers

Match the following antidepressants with their effects on prolactin levels:

Bupropion = May decrease prolactin SSRI = Generally no change in prolactin Mirtazapine = No effect on prolactin SNRIs = Clear association with increased prolactin Signup and view all the answers

Which of the following antidepressants has no recorded changes in prolactin levels during clinical trials?

Both B and C Signup and view all the answers

Reports of galactorrhea are associated only with SSRIs.

False Signup and view all the answers

Identify one antidepressant that may increase prolactin levels according to case reports.

Fluoxetine Signup and view all the answers

Having diabetes increases the odds of co-morbid depression by 50%.

False Signup and view all the answers

SSRIs are recommended as a first-line treatment for depression in diabetic patients.

True Signup and view all the answers

Antidepressants do not have any impact on metabolic control in diabetic patients.

False Signup and view all the answers

Patients on antidepressants may show reduced adherence to their antidiabetic medications.

True Signup and view all the answers

Monitoring blood glucose is unnecessary when initiating antidepressant treatment.

False Signup and view all the answers

Which antidepressant class is likely to have a favorable effect on diabetic parameters in patients with type II diabetes?

SSRIs Signup and view all the answers

Mirtazapine is associated with an increase in body mass index (BMI) in diabetic patients.

True Signup and view all the answers

Which antidepressant class does NOT appear to disrupt glycemic control?

SNRIs Signup and view all the answers

Clomipramine is reported to precipitate __________.

diabetes Signup and view all the answers

Match the following antidepressants with their effects on glucose homeostasis:

SSRIs = Favorable effects on glycemic control TCAs = Increased appetite and hyperglycemia MAOIs = Extreme hypoglycemic episodes Mirtazapine = Increase in BMI and HbA1c worsening Signup and view all the answers

Which of the following antidepressants has shown improvement in HbA1c levels?

Fluoxetine Signup and view all the answers

Long-term use of TCAs is linked to a lower risk of developing diabetes.

False Signup and view all the answers

What is a common side effect associated with the use of irreversibly acting MAOIs?

Weight gain Signup and view all the answers

Studies suggest that __________ has little influence on glycemic control in diabetic neuropathy.

duloxetine Signup and view all the answers

Which of the following antidepressants is associated with an increased risk of type 2 diabetes?

Trazodone Signup and view all the answers

The prevalence of sexual dysfunction is higher in patients whose depression does not remit after citalopram treatment compared to those whose depression does remit.

True Signup and view all the answers

All antidepressants have the potential to cause sexual dysfunction, but the rates of this side effect are the same across all types.

False Signup and view all the answers

Sexual dysfunction associated with antidepressants is generally considered to be irreversible.

False Signup and view all the answers

The drug dapoxetine is specifically licensed for the treatment of premature ejaculation in many countries.

True Signup and view all the answers

Post-SSRI sexual dysfunction is a well-understood condition with a clear prevalence and pathophysiology.

False Signup and view all the answers

Management strategies for sexual dysfunction from antidepressants are considered universally ideal without the need for individual assessment.

False Signup and view all the answers

Sexual dysfunction is only caused by prescribed drug treatment.

False Signup and view all the answers

Patients taking antidepressants generally experience a uniform response in terms of sexual side effects.

False Signup and view all the answers

Patients with depression are more likely to have obesity, diabetes, and cardiovascular disease compared to the general population.

True Signup and view all the answers

Direct questioning about sexual functioning is less effective than relying on spontaneous patient reporting.

False Signup and view all the answers

40-50% of individuals with depression experience diminished libido before starting antidepressant treatment.

True Signup and view all the answers

Only around 15-20% of those with depression face orgasm problems before they begin taking antidepressants.

True Signup and view all the answers

Baseline sexual functioning should be assessed prior to prescribing antidepressants.

True Signup and view all the answers

Complaints of sexual dysfunction may indicate progression of underlying medical or psychiatric conditions.

True Signup and view all the answers

Patients with depression rarely have issues related to desire and arousal as a result of depression itself.

False Signup and view all the answers

Which antidepressant is associated with low rates of sexual dysfunction compared to others?

Bupropion Signup and view all the answers

MAOIs are linked to high rates of sexual dysfunction.

False Signup and view all the answers

Name the antidepressant associated with erectile dysfunction and disorders of ejaculation but is uncertain regarding sexual desire.

Levomilnacipran Signup and view all the answers

__________ is known for causing anorgasmia at comparatively lower rates.

Fluvoxamine Signup and view all the answers

Match the antidepressants with their impact on sexual desire:

Agomelatine = Similar to placebo Reboxetine = Probably less than SSRIs/SNRIs Trazodone = Reportedly low Moclobemide = Low risk of SD Signup and view all the answers

Which of the following antidepressants has a similar sexual dysfunction rate as some SSRIs?

Duloxetine Signup and view all the answers

Trazodone is commonly reported to increase sexual desire.

True Signup and view all the answers

What common side effect does Duloxetine have in relation to sexual function?

Sexual desire and orgasm dysfunction Signup and view all the answers

The sexual dysfunction rate of __________ is reported to be similar to placebo for Agomelatine.

Sexual desire, arousal, and orgasm Signup and view all the answers

Match the following antidepressants with their sexual dysfunction characteristics:

MAOIs = 20% to 42% incidence of SD Bupropion = Low rates compared to others SSRIs = Generally high rates of SD Mirtazapine = Causes less SD than SSRIs Signup and view all the answers

Which antidepressant is associated with high rates of sexual dysfunction but has also shown isolated case reports of increased libido and orgasms?

Venlafaxine Signup and view all the answers

Vortioxetine has a common incidence of sexual dysfunction at doses of 10mg/day or less.

False Signup and view all the answers

What sexual function effects are associated with Tricyclics according to the analysis?

Common sexual desire, arousal, and orgasm Signup and view all the answers

The antidepressant Vilazodone has a sexual desire rating of __________.

<ul> <li></li> </ul> Signup and view all the answers

Match the following antidepressants with their sexual drive ratings:

Tricyclics = ++ Venlafaxine = ++ Vilazodone = + Vortioxetine = - Signup and view all the answers

Which of the following antidepressants is considered to have a more favorable sexual side effect profile?

Agomelatine Signup and view all the answers

Waiting for spontaneous remission is considered the most effective method for managing sexual adverse effects from antidepressants.

False Signup and view all the answers

List two non-pharmacological treatment strategies for managing sexual adverse effects.

Dose reduction, Drug holidays Signup and view all the answers

Lower risk antidepressants include , , and __.

bupropion, mirtazapine, vortioxetine Signup and view all the answers

Match the following strategies for managing antidepressant-related sexual adverse effects to their descriptions:

Rule out causes = Consideration of other factors affecting sexual functioning Switching medication = Changing to a lower risk antidepressant Dose reduction = Reducing dosage in patients at full remission Drug holidays = Missed doses prior to sexual activity Signup and view all the answers

Which medications could be implicated as causing sexual dysfunction?

All of the above Signup and view all the answers

Intermittently missing one or two doses before planned sexual activity is a widely accepted effective method.

False Signup and view all the answers

What potential risks are associated with drug holidays?

Discontinuation symptoms Signup and view all the answers

The percentage of patients that may experience spontaneous remission is to percent.

5, 10 Signup and view all the answers

Which of the following is a possible treatment strategy when managing patients with sexual adverse effects?

Wait for spontaneous remission Signup and view all the answers

Which pharmacological treatment has shown to improve sexual function in men with antidepressant-related erectile dysfunction?

Sildenafil Signup and view all the answers

Transdermal testosterone has been proven ineffective for improving sexual functioning in women with lower libido due to SSRIs/SNRIs.

False Signup and view all the answers

What is the main finding regarding the use of Bupropion in women?

Higher doses (300mg/day) may be useful for sexual dysfunction. Signup and view all the answers

Both flibanserin and _______ are FDA-approved for the treatment of HSDD in premenopausal women.

bremelanotide Signup and view all the answers

Match the following agents with their effects:

Aripiprazole = Improved sexual functioning and desire in women Brexpiprazole = Modest improvement in sexual functioning Pimavanserin = Improved sexual functioning as an add-on treatment Buspirone = Effective for citalopram or paroxetine-induced dysfunction Signup and view all the answers

Which statement is true regarding the effectiveness of mirtazapine for sexual dysfunction?

Some studies suggest benefits while others show negative results. Signup and view all the answers

Yohimbine has been found to be effective in treating medication-induced sexual dysfunction.

True Signup and view all the answers

What is one of the main findings regarding the use of augmenting agents like aripiprazole in treatment-resistant depression?

It improved sexual functioning and desire in women. Signup and view all the answers

Recent studies have shown mixed results for the effectiveness of _______ on SSRI-induced sexual dysfunction.

Amantadine Signup and view all the answers

What is a significant limitation of many other agents studied for antidepressant-induced sexual dysfunction?

Evidence for their effectiveness is limited. Signup and view all the answers

The use of gastro-protective drugs significantly eliminates the risk of GI bleeds associated with SSRIs.

False Signup and view all the answers

Patients who take SSRIs have an increased risk of being admitted to the hospital for upper gastrointestinal bleeding.

True Signup and view all the answers

Combined use of SSRIs and NSAIDs quadruples the risk of gastrointestinal bleeding.

True Signup and view all the answers

SSRIs do not affect the risk of lower GI bleeding.

False Signup and view all the answers

SSRIs can reduce the risk of minor cardiac events in patients treated for acute coronary syndromes.

True Signup and view all the answers

SSRIs increase the risk of bleeding events by depleting serotonin in platelets.

True Signup and view all the answers

After discontinuing SSRIs, the excess risk of bleeding remains the same as during treatment.

False Signup and view all the answers

The relative risk of any bleeding event with SSRIs is around 2.0.

False Signup and view all the answers

SSRIs are known to decrease gastric acid secretion, thus reducing the risk of peptic ulcers.

False Signup and view all the answers

SSRIs show no increased risk of bleeding when prescribed with direct-acting anticoagulants.

False Signup and view all the answers

The risk of abnormal bleeding with SSRIs is highest during the first month of treatment.

True Signup and view all the answers

Upper gastrointestinal bleeding is a known risk associated with SSRIs.

True Signup and view all the answers

SSRIs were found to cause the same rate of gastrointestinal bleeding as traditional antidepressants.

False Signup and view all the answers

The absolute risk of bleeding events from SSRIs is estimated to be between 0.5% and 6%.

True Signup and view all the answers

Serotonin released from platelets promotes vasodilation and reduces clot formation.

False Signup and view all the answers

Which antidepressants are known for strong serotonin reuptake inhibition? (Select all that apply)

Sertraline Signup and view all the answers

Which antidepressants have intermediate serotonin reuptake inhibition? (Select all that apply)

Escitalopram Signup and view all the answers

Which of the following antidepressants are associated with weak or no serotonin reuptake inhibition? (Select all that apply)

Lofepramine Signup and view all the answers

Age over ______ is a risk factor for bleeding with SSRIs.

65 Signup and view all the answers

Which of the following factors is NOT a risk factor for bleeding with SSRIs?

Being under 18 Signup and view all the answers

Coronary artery disease is a risk factor for bleeding with SSRIs.

True Signup and view all the answers

What is the absolute risk of upper gastrointestinal bleeding (UGIB) when using Aspirin with an SSRI?

6% Signup and view all the answers

The absolute risk of lower gastrointestinal bleeding (LGIB) is the same whether taking an SSRI alone or with an NSAID.

False Signup and view all the answers

What is the absolute risk percentage of UGIB with SSRIs alone?

2% Signup and view all the answers

The absolute risk of upper gastrointestinal bleeding when using Warfarin with an SSRI is __________.

4% Signup and view all the answers

Match the drug combination with its absolute risk of upper gastrointestinal bleeding (UGIB):

Aspirin + SSRI = 6% Warfarin + SSRI = 4% NSAID + SSRI = 3% SSRI alone = 2% Signup and view all the answers

What is the absolute risk of intracranial hemorrhage when using SSRIs alone according to the study by Shin et al?

1 in 632 Signup and view all the answers

The risk of intracranial hemorrhage is highest when SSRIs are combined with NSAIDs.

True Signup and view all the answers

What is the risk of intracranial hemorrhage associated with an antidepressant when combined with an anticoagulant according to Renoux et al?

1 in 260 Signup and view all the answers

The annual risk of intracranial hemorrhage for older patients using SSRIs is ____ (expressed as 1 in X).

1 in 240 Signup and view all the answers

Match the following studies with their reported risks of intracranial hemorrhage:

Shin et al = 1 in 632 (0.16%) Renoux et al = 1 in 260 (0.38%) Smoller et al = 1 in 240 (0.42%) Signup and view all the answers

What was the prevalence of menstrual disorder in patients taking SSRIs compared to those who did not take antidepressants?

24.6% Signup and view all the answers

The use of antidepressants has been associated with an increased risk of postpartum hemorrhage (PPH).

True Signup and view all the answers

What percentage of women who did not take antidepressants experienced postpartum hemorrhage (PPH)?

8.7% Signup and view all the answers

The absolute risk of postpartum anemia after a non-surgical vaginal delivery in women who were current users of SSRIs is __________.

12.8% Signup and view all the answers

Which antidepressants were mentioned as being associated with abnormal vaginal bleeding?

All of the above Signup and view all the answers

What is the increased risk factor of postpartum hemorrhage (PPH) in women taking psychoactive medications compared to those who are not?

Match the antidepressant to its associated bleeding risk:

SSRIs = Increased menstrual disorder prevalence Venlafaxine = Reported abnormal bleeding cases Mirtazapine = Higher risk of PPH Bupropion = Not consistently linked to bleeding Signup and view all the answers

SSRIs are the only class of antidepressants associated with an increased risk of various types of bleeding.

False Signup and view all the answers

The study found that women taking antidepressants experienced lower blood loss during delivery than those not taking them.

False Signup and view all the answers

What was the average blood loss during delivery for women who took SSRIs?

484mL Signup and view all the answers

What is one alternative to SSRIs that may have minimal effects on measurable clotting mechanisms?

Mirtazapine Signup and view all the answers

Preoperative treatment with __________ has been recognized as an independent risk factor for blood transfusion in elective surgery.

SSRIs Signup and view all the answers

Match the following antidepressants with their bleeding risk:

SSRIs = Increased risk of GI bleeding Mirtazapine = Increased risk of UGI bleeding Bupropion = Minimal effects on clotting mechanisms Duloxetine = No effect on bleeding risk Signup and view all the answers

What should be avoided when prescribing SSRIs to patients?

Medication history of GI bleeds Signup and view all the answers

It is safe to co-prescribe SSRIs with oral anticoagulants without any precautions.

False Signup and view all the answers

Hypericins alone are proven to effectively treat depression.

False Signup and view all the answers

The majority of St. John's Wort (SJW) preparations are considered to be of high quality.

False Signup and view all the answers

SJW is known to cause severe phototoxic reactions in all patients.

False Signup and view all the answers

The effectiveness of SJW has been confirmed for long-term depression treatment.

False Signup and view all the answers

Hyperforin in SJW can affect drug metabolism due to its inductive properties.

True Signup and view all the answers

Caution is recommended when using high doses of SJW, especially in individuals with a history of bipolar disorder.

True Signup and view all the answers

Adverse effects associated with SJW are generally more frequent than those with older antidepressants.

False Signup and view all the answers

St. John's Wort contains a combination of at least 10 different components, including hypericin and hyperforin.

True Signup and view all the answers

The active ingredient of St. John's Wort for treating depression has been definitively identified.

False Signup and view all the answers

Studies have shown that St. John's Wort is as effective as standard antidepressants for treating mild-to-moderate depression.

True Signup and view all the answers

The evidence supporting St. John's Wort is universally reliable regardless of the geographical location of the studies.

False Signup and view all the answers

There is substantial evidence for the efficacy of St. John's Wort in treating severe depression.

False Signup and view all the answers

St. John's Wort preparations are often standardized based on their total content of hypericins.

True Signup and view all the answers

St. John's Wort has been licensed in Germany for the treatment of anxiety disorders.

False Signup and view all the answers

Certain pain syndromes have shown strong evidence for treatment with St. John's Wort.

False Signup and view all the answers

Which antidepressant is known to cause the most severe sedation and sexual dysfunction?

Tricyclics Signup and view all the answers

All SSRIs cause sexual dysfunction as a side effect.

False Signup and view all the answers

Which antidepressant type is associated with cardiac conduction disturbances?

Tricyclics Signup and view all the answers

The antidepressant __________ is known to have both sedation and postural hypotension as common side effects.

Mirtazapine Signup and view all the answers

Match the following antidepressants with their respective severity of sedative effects:

Amitriptyline = Severe Citalopram = None Duloxetine = Absence Venlafaxine = None Signup and view all the answers

Which drug has been identified to cause nausea/vomiting as a common side effect?

Duloxetine Signup and view all the answers

Trazodone causes anticholinergic effects.

False Signup and view all the answers

Identify one antidepressant from the table that has no sedative effects.

Agomelatine Signup and view all the answers

The abbreviation SNRI stands for __________ and is associated with Duloxetine and Venlafaxine.

Serotonin-Norepinephrine Reuptake Inhibitor Signup and view all the answers

Study Notes

Introduction to Depression

Depression is recognized as a global health concern.
Antidepressants are the primary treatment, while therapy is a primary option for milder forms.
Other treatment methods, such as VNS and rTMS exist but are not widely available.

Prescription of antidepressants

Patients should be involved in choosing a drug and considering non-pharmacological methods.
Antidepressants may take several weeks to have an effect.
Dosage should be sufficient but carefully adjusted.
Treatment should continue for at least 6-9 months after resolution of symptoms.
Antidepressants should be withdrawn gradually, informing patients of possible discontinuation symptoms.

NICE guidelines on depression treatment

Antidepressants are not recommended as a first-line treatment for mild, recent onset depression; active monitoring, self help or CBT is preferred.
Antidepressants are recommended for moderate to severe depression and dysthymia.
Generic SSRIs are recommended.
All patients should be informed about the possibility of withdrawal symptoms from antidepressants.
Treatment-resistant depression may be treated with augmentation with lithium or an antipsychotic, or with a second antidepressant.
Patients with two prior episodes and functional impairment should be treated for at least two years.
Electroconvulsive therapy (ECT) is supported for severe and treatment-resistant depression.

Antidepressants

All antidepressants have demonstrated greater effectiveness than placebo in treating adults with major depressive disorder.
Studies demonstrate equal benefit with antidepressants for mild, moderate, or severe major depression.
Antidepressants are generally recommended for moderate to severe depression, with psychological treatments being preferred for milder forms.
Approximately 20% of moderate-severe depression patients recover without treatment, 30% respond to placebo, and 50% respond to antidepressant treatment.
The antidepressant effect is statistically evident within 1 week in large studies, and typically observed within 2 weeks in clinical settings.
Patients with no improvement after 3-4 weeks may not respond to the prescribed drug at that dose.
Patients showing minor improvements at 4 weeks may go on to respond fully.

Choice of antidepressant and relative side effects

SSRIs are generally well-tolerated and are recommended as a first-line pharmacological treatment.
There is evidence that some antidepressants may be more effective overall, but this needs further validation.
Antidepressants have varying side effect profiles. For example, paroxetine is associated with weight gain and sexual dysfunction.
Dual re-uptake inhibitors, such as venlafaxine and duloxetine, tend to be tolerated less well than SSRIs.
SSRIs are associated with side effects, including sexual dysfunction, hyponatraemia, and gastrointestinal bleeds.
TCAs have adverse cardiovascular effects and are particularly toxic in overdose.
MAOIs can interact with tyramine-containing foods to cause hypertensive crisis or hypotension.
All antidepressant drugs can cause discontinuation symptoms, more likely with short half-life drugs.

Drug interactions

Some SSRIs are potent inhibitors of cytochrome P450 (CYP) pathways, leading to potential drug interactions.
For example, fluvoxamine inhibits CYP1A2 resulting in increased theophylline levels, and fluoxetine inhibits CYP2D6 leading to increased seizure risk.

Drug Interactions

Fluoxetine and paroxetine are potent inhibitors of CYP2D6 and can cause adverse interactions with other drugs, including potential increased seizure risk with clozapine and treatment failure with tamoxifen leading to increased mortality
Antidepressants can also cause pharmacodynamic interactions. For example, the cardiotoxicity of TCAs may be exacerbated by diuretics
Potential pharmacokinetic and pharmacodynamic interactions between antidepressants have to be considered when switching antidepressants.

Suicidal Thoughts

Antidepressant treatment has been associated with an increased risk of suicidal thoughts and acts, particularly in adolescents and young adults
Suicide and self-harm rates are higher when antidepressants are started or stopped
Switching antidepressants may be a marker of increased risk of suicidal behaviors in those who initiate antidepressant treatment aged 75 years and over.
All antidepressants have been implicated, including those marketed for an indication other than depression.
While the relative risk may be elevated above placebo rates in some patient groups, the absolute risk remains very small.
The most effective way to prevent suicidal thoughts and acts is to treat depression; antidepressant drugs are the most effective treatment currently available.
Suicidality is greatly reduced by the use of antidepressants, but those experiencing treatment-emergent or worsening suicidal ideation with one antidepressant may be more likely to have a similar experience with subsequent treatments.
Recent data suggests that an increasing proportion of young women who later committed suicide had been treated with antidepressants prior to and at the time of the suicide.
There is no clear consensus on the potential dangers of antidepressants except that young people are most at risk.

Toxicity in Overdose

Toxicity in overdose varies both between and within groups of antidepressants.

Duration of Treatment

Antidepressants relieve the symptoms of depression but do not treat the underlying cause.
Antidepressants should be taken for 6–9 months after recovery from a single episode.
There is evidence of benefit from maintenance treatment for at least 2 years in patients who have had multiple episodes.
There are little data on which to base recommendations about the duration of treatment of augmentation regimens.
Some evidence suggests that antidepressants worsen outcome in the long term.

Next Step Treatments

Approximately a third of patients do not respond to the first antidepressant prescribed.
Options for non-responders include dose escalation, switching to a different drug, and a number of augmentation strategies.
There is no clear difference in effectiveness between strategies.

Anxiety Spectrum Disorders

Antidepressants are first-line treatments in a number of anxiety spectrum disorders.

Tricyclics

Lofepramine effective dose is at least 75-100mg/day, possibly 125mg/day.
140mg/day lofepramine may also be effective.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Citalopram minimum effective dose - 20mg/day
Escitalopram minimum effective dose - 10mg/day
Fluoxetine minimum effective dose - 20mg/day
Fluvoxamine minimum effective dose - 50mg/day
Paroxetine minimum effective dose - 20mg/day
Sertraline minimum effective dose - 50mg/day

Other Antidepressants

Agomelatine minimum effective dose - 25mg/day
Bupropion minimum effective dose - 150mg/day
Desvenlafaxine minimum effective dose - 50mg/day
Duloxetine minimum effective dose - 60mg/day
Levomilnacipran minimum effective dose - 40mg/day
Mirtazapine minimum effective dose - 30mg/day, possibly 15mg/day
Moclobemide minimum effective dose - 300mg
Reboxetine minimum effective dose - 8mg/day
Trazodone minimum effective dose - 150mg/day
Venlafaxine minimum effective dose - 75mg/day
Vilazodone minimum effective dose - 20mg/day
Vortioxetine minimum effective dose - 10mg/day

Drug Treatment of Depression

Step 1: Discuss Drug Choice with Patient
- Discuss potential benefits and side effects of medication.
- Discuss likelihood of discontinuation symptoms and the time to see results.
- Emphasize the importance of a strong patient-therapist relationship for successful treatment.
- SSRIs are often the first-line treatment.
- Consider mirtazapine if the patient needs help with sedation.
Step 2: Initiate Antidepressant Treatment
- Start taking the antidepressant.
- Adjust the dosage as needed to reach a therapeutic level.
- Evaluate treatment progress after two weeks.
Step 3: Monitor and Adjust Treatment
- Monitor treatment response weekly for one to two weeks.
- If there is no response, consider increasing the dosage.
- If the treatment is effective, continue for 6-9-2-4 months.
- Long-term treatment may be considered for recurrent depression – 2-6 months.
- If the treatment is ineffective or poorly tolerated, switch to a different antidepressant.
- Titrate the dosage of the new medication to a therapeutic level.
- Assess efficacy for 3-4 weeks, and increase the dosage if needed.
- If poorly tolerated or ineffective, consider other options.
Step 4: Alternative Treatment Options
- Consider using mirtazapine, vortioxetine, or agomelatine if other options have failed.
- If treatment remains resistant, refer the patient to other treatment options for resistant depression.

Antidepressant Selection and Monitoring

Tools for assessing drug effect: Montgomery–Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS), Patient Health Questionnaire-9 (PHQ-9)
Most authorities recommend SSRI or mirtazapine for sedation
Largest network meta-analysis: Drugs with effects on both norepinephrine and serotonin uptake are most effective; agomelatine and SSRIs have lowest dropout rates.
Assessment at 2 weeks somewhat useful for outcome prediction: only ~30% of those not reaching improvement threshold at 2 weeks will ultimately respond; even fewer respond if no improvement or deterioration at 2 weeks.
Switching between drug classes in cases of poor tolerability is supported. In practice, many patients tolerate one SSRI after not tolerating another.
Switching within a drug class is effective, although switching between classes is more common.
APA recommends both switching within and between drug classes.
NICE draft guidelines suggest little evidence for switching, better support for combining antidepressants or adding a second-generation antipsychotic.
Strongest evidence for switching after failure of one treatment is for vortioxetine.
Limited evidence for increasing dose of most SSRIs, especially when severity measured with total rating scale scores.
Some evidence suggests increasing venlafaxine, escitalopram, and tricyclics may be helpful.
Gains in efficacy from dose increases are generally small or non-existent.

Managing Treatment-Resistant Depression

Treatment-resistant depression is difficult to treat successfully with often poor outcomes.
STAR*D program uses remission of symptoms as its main outcome.
Stage 1 of STAR*D: citalopram showed remission in 28% of subjects at 14 weeks.
STAR*D demonstrated a flexible approach is required for resistant depression.
STAR*D established bupropion and buspirone augmentation as worthwhile options.
STAR*D confirmed safety and efficacy of mirtazapine and venlafaxine combination.
Criticisms of STAR*D program: absence of placebo group, open nature of treatment, non-accounting for withdrawal after first visit, unexplained use of a priori secondary measure as main outcome, payment to subjects, high relapse rate at 12 month follow-up.

General Antidepressant Management

Switch treatments early if adverse effects are intolerable or no improvement is seen by 3-4 weeks.
Antidepressants have a fairly prompt onset of action.
Non-response at 2-6 weeks is a good predictor of overall non-response.
Absence of any improvement at 3-4 weeks should normally provoke a change in treatment. BAP guidelines suggest 4 weeks.
If there is some improvement at 3-4 weeks, continue and assess for a further 2-3 weeks.

Treatment-Resistant Depression - First Choice Treatments

Aripiprazole
- Add aripiprazole to current antidepressant (2-20 mg/day)
- Well supported by research
- Usually well tolerated and safe
- Low doses (2-10 mg/day) may be effective
- Common side effects: akathisia and restlessness at doses above 10mg/day, insomnia
Lithium
- Add lithium to current antidepressant
- Well-established and supported by research recommendations from NICE
- May be better tolerated at lower plasma levels
- Potential toxicity issues
- Specialist referral and plasma level monitoring required
- May not be effective in patients resistant to multiple treatments
Olanzapine and Fluoxetine
- Combine olanzapine and fluoxetine (6.25-12.5mg + 25-50mg daily)
- Well researched
- Typically well tolerated
- Weight gain is a risk
- Limited clinical experience outside of the USA
- Most research is focused on bipolar depression
Quetiapine
- Add quetiapine (150mg or 300mg a day) to SSRI/SNRI
- Well supported by research
- Usually well tolerated
- Possible for dry mouth, sedation, constipation, and longer-term weight gain
Bupropion
- Add bupropion (up to 400mg/day) to SSRI
- Supported by STAR*D research
- Usually well tolerated
- May improve sexual adverse effects
- Not licensed for depression in the UK
- Potential risk of serotonin syndrome
Mianserin or Mirtazapine
- Add mianserin (30mg/day) or mirtazapine (30-45mg/day) to SSRI or venlafaxine
- Recommended by NICE
- Usually well tolerated
- Risk of blood dyscrasia with mianserin
- Weight gain and sedation with mirtazapine
- Recent large RCT shows no advantage for mirtazapine + SSRIs/SNRIs in prior non-response

Second Choice Treatments for Treatment-Resistant Depression

Ketamine (0.5mg/kg IV over 40 minutes)
- Rapid response (within hours)
- High remission rate
- Repeated doses may maintain response
- Well tolerated at sub-anaesthetic dose
- Must be administered in a hospital setting
- Potential cognitive effects (confusion, dissociation) and psychiatric symptoms
- May increase blood pressure, heart rate, and cause arrhythmias
- Requires pre-treatment ECG
- Adverse effects may be underestimated
- May require repeated treatment to maintain effect
- Intranasal esketamine is licensed in most countries (dose 28-84mg)
Lamotrigine (100mg, 200mg, 400mg daily)
- Well researched
- Widely used
- Well tolerated augmentation strategy
- Well established
- Effective
- Well supported in the literature
- Slow titration process
- Risk of rash
- Appropriate dosing is unclear
Electroconvulsive Therapy (ECT)
- Well established
- Effective
- Well supported in the literature
- Poor public perception
- Requires general anesthesia
- Specialist referral is required
- Usually reserved for last-line treatment, rapid response needs, or in combination with other treatments
Tri-iodothyronine (20-50µg/day)
- Usually well tolerated
- Supported by some literature
- May be effective in bipolar depression
- Requires clinical and biochemical thyroid function testing
- Specialist referral usually required
- Some negative studies exist
- No advantage over antidepressants alone in non-refractory illness

Treatment-Resistant Depression - Other Treatments

There are numerous treatments investigated for treatment-resistant depression, with limited supportive evidence.
Amantadine (up to 300mg/day): Limited data supports its efficacy.
Ayahuasca: Demonstrated effectiveness for treatment but requires specialized use by professionals.
Buprenorphine (0.8-2mg/day): Reasonable evidence supports its use, but potential contraindications exist.
Carbergoline 2mg/day: Very limited data available for this treatment.
D-cycloserine 1000mg/day: A small randomized controlled trial (RCT) suggests a positive effect.
Dexamethasone 3-4mg/day: Limited research supports its use.
Dextromethorphan + Quinidine 45/10mg BD: Promising novel treatment as an NDMA antagonist. Quinidine is crucial for extending the action of dextromethorphan due to its CYP2D6 inhibitor properties. Possible benefit but research quality is limited.
Folate/methyl folate 12-14 (2mg/day folate?): Further clarification on mechanism of action and dosage is needed.
Hyoscine (Scopolomine) (4mcg/kg IV): A growing body of research suggests a rapid and significant impact of this treatment.
Ketoconazole 400-800mg/day: Rarely used due to the risk of hepatotoxicity.
MAOIs and TCAs (e.g. trimipramine and phenelzine): Previously widely used therapies with a requirement for careful monitoring.
Mecamylamine up to 10mg/day: One small pilot study (21 patients) explored its potential effectiveness.
Minocycline 200mg/day: Several positive meta-analyses in both animal and human studies showed promise. A recent failed RCT in bipolar depression raises questions about its application in all cases.
Modafinil 100-400mg/day: Further research is needed to determine its effectiveness.
Naltrexone 100mg/day: No studies exist for non-opiate misusers.
Nemifitide 40-240mg/day SC: One pilot study involving 25 patients explored its potential.
Nortriptyline & lithium: Re-emerging as a treatment option.
Oestrogens: Limited data supports its use for treatment-resistant depression.

Treatment Options for Depression

Omega-3-triglycerides EPA18: Often included in antidepressant therapy. Effectiveness depends on dosage - a total dose of 60% is recommended.
Pindolol19: Available in primary care, administered at 5mg three times a day or 7.5mg once daily. Data mainly focuses on response acceleration, and evidence regarding refractory depression is mixed.
Pramipexole19: Dosage ranges from 0.125-5mg per day. Supported by one robust RCT, indicating a clear effect.
Psilocybin18: Administered in two doses (10/25mg) a week apart. Effective, but reserved for specialized use.
Risperidone51: Typically combined with antidepressants, dosage ranges from 0.5-3mg per day. Less robust RCT support compared to other SGAs.
S-adenosyl-l-methionine19: Available in oral and intravenous forms, with dosages at 1600mg/day and 400mg/day respectively. Limited data in treatment-resistant depression. Weakly supported by a Cochrane review16.
SSRI + Buspirone16,43: Administered up to 60mg per day, supported by the STAR*D study.
SSRI + TCA18: Requires higher doses and is poorly tolerated (dizziness is common).
Stimulants (amfetamine, methylphenidate49): Widely used in the past, with varying outcomes. Refer to "Psychostimulants in Depression" section for further details.
TCA - High Doses: Previously a common treatment. Essential to monitor cardiac health.
Testosterone Gel10: Effective for individuals with low testosterone levels.
Tianeptine: Limited data available. Availability varies across countries.
Tryptophan19,46: Administered at 2-3g three times a day, a long history of successful use.
Venlafaxine10: Dosage above 200mg per day, can be initiated in primary care. Recommended by NICE1. Nausea, vomiting, and discontinuation symptoms are common. Essential to monitor blood pressure.
Venlafaxine - Very High Dose (up to 600mg/day): Refer to previous entry. Crucial to monitor cardiac health.
Venlafaxine + IV clomipramine3: Essential to monitor cardiac health. One RCT (n=60) showed promising results in refractory depression.
Zinc48: Dosage: 25mg Zn+/day.
Ziprasidone11: Limited support, likely lacking antidepressant effects.

Ketamine: A Novel Antidepressant

Ketamine, an NMDA receptor antagonist and dissociative anesthetic, has emerged as an effective rapid-acting antidepressant.
In 2000, a study found a single subanesthetic dose of IV ketamine (0.5mg/kg over 40 minutes) produced a significant antidepressant effect within hours that lasted up to 3 days.
This finding has been replicated in several trials for both unipolar and bipolar depression, including treatment-resistant individuals.
Esketamine, an enantiomer of ketamine that binds more potently to the NMDA receptor, is now approved for use in TRD in Europe and the United States as a nasal spray.

Mechanism of Action

The precise mechanisms of ketamine's antidepressant effects are still being researched.
It's hypothesized that ketamine blocks NMDA receptors on GABAergic interneurons, leading to a surge of glutamate in the cortex.
This glutamate surge activates AMPA receptors, potentially contributing to synaptogenesis and neuroplasticity.

Routes of Administration

The optimal route of administration for TRD is not fully established.
IV ketamine (0.5mg/kg over 40 minutes) is considered the gold standard with the most supporting evidence.
Other routes include SC, IM, oral, and SL, but further research is needed to determine their efficacy and safety.
Each route has its own advantages and challenges in terms of bioavailability, duration of effect, practicality, and patient comfort.

Adverse Effects

Ketamine commonly causes dissociative symptoms at antidepressant doses, including perceptual distortions and anxiety.
Patients should be monitored by a trained clinician during and after administration.
Ketamine can induce laryngospasm, so the observing clinician should be trained in advanced life support.
Lower doses administered orally or sublingually may produce less intense dissociative symptoms, allowing for home administration after initial supervision.
Patients should be advised to avoid driving, operating machinery, and high-risk activities after administration.
Prescribing clinicians must consider the risks of diversion and illegal use.
Ketamine can affect blood pressure and heart rate, so a physical examination and monitoring are recommended before and after administration.

Psychotic Depression

Psychotic depression is an under-identified and serious form of depression, accounting for up to 1% of lifetime risk.
Patients with psychotic depression generally experience more severe symptoms compared to those without psychotic features.
Combined treatment with an antidepressant and antipsychotic is often recommended as first-line therapy.
Tricyclic antidepressants (TCAs) are likely more effective than newer antidepressants in treating psychotic depression.
Prior treatment failures reduce the likelihood of responding to subsequent treatment.
Studies suggest that combining olanzapine and fluoxetine, or olanzapine and sertraline, can be effective.
Augmenting antidepressants with quetiapine, aripiprazole, or amisulpride has also shown promising results.
Venlafaxine plus quetiapine has been found to be more effective than venlafaxine alone.
Reviews and meta-analyses highlight the superiority of combined antipsychotic and antidepressant therapy.
While combining an antidepressant and antipsychotic is recommended for acute episodes, the optimal duration of such combined treatment remains unclear.
There is evidence suggesting that discontinuing antipsychotic treatment during the maintenance phase after resolution of the acute illness may worsen outcomes.
It is important to be mindful of the potential for weight gain associated with certain antipsychotic medications, particularly in younger patients.
Under-diagnosis and under-treatment of psychotic depression are significant issues.
Some antipsychotic medications, like quetiapine and olanzapine, have beneficial antidepressant effects.
Long-term outcomes tend to be less favorable for individuals with psychotic depression compared to non-psychotic depression.
Psychotic depression involves a greater risk of suicide attempts and completions compared to non-psychotic depression.
Electroconvulsive therapy (ECT) is a viable treatment option for psychotic depression, often demonstrating greater effectiveness and reduced relapse risk compared to non-psychotic depression.
Antiglucocorticoid strategies, targeting HPA axis hyperactivity, are another approach.
Mifepristone, a glucocorticoid receptor antagonist, has shown potential but requires further investigation.
Anecdotal reports suggest the potential benefit of methylphenidate, lamotrigine, and combined phenelzine, aripiprazole, and quetiapine.
Minocycline has also demonstrated positive effects in open studies.
Ketamine could also be effective in treating psychotic depression.
TCAs are generally considered the first-line treatment.
SSRIs or SNRIs are a second-line option when TCAs are not well-tolerated.
Augmenting an antidepressant with olanzapine or quetiapine is recommended.
Optimum dose and duration of antipsychotic augmentation remain unknown.
Discontinuing the antipsychotic during maintenance is generally advised, although some evidence suggests this may worsen outcomes.
ECT should be considered when rapid responses are required or other treatments have failed.

Switching Antidepressants: General Guidelines

Abrupt withdrawal should be avoided when switching antidepressants unless there is a serious adverse event.
Cross-tapering is preferred, where the dose of the ineffective drug is slowly reduced while the new drug is slowly introduced.
The speed of cross-tapering is best judged by monitoring the patient's tolerability, as studies are limited.
Extended periods of cross-tapering may be needed to mitigate withdrawal symptoms.
Co-administration of certain antidepressants is contraindicated, even when cross-tapering.
Switching strategy depends on the reason for switching (inadequate response, poor tolerability, adverse effects) and the pharmacokinetic and pharmacodynamic properties of the drugs involved.
Cross-tapering may not be necessary when switching from one SSRI to another, as their effects are similar.
Abrupt cessation might be acceptable when switching to a drug with a similar, but not identical, mode of action.
Abruptly stopping one antidepressant and starting another at the usual dose might be well tolerated and may reduce the risk and severity of discontinuation symptoms.
Potential dangers of simultaneously administering two antidepressants include:
- Pharmacodynamic interactions (serotonin syndrome, hypotension, drowsiness)
- Pharmacokinetic interactions (e.g., elevation of tricyclic plasma levels by some SSRIs)
Agomelatine does not seem to be associated with a discontinuation syndrome, but slow withdrawal is recommended when switching.
Agomelatine is not expected to mitigate discontinuation reactions of other antidepressants due to its mode of action.
While there is no theoretical basis for pharmacodynamic interactions between agomelatine and other antidepressants, data is limited, so caution is advised.
Pharmacokinetic interactions do occur with agomelatine, and it should not be administered with fluvoxamine.
Serotonin syndrome can occur with a single serotonergic drug at therapeutic dose or more frequently in combination of serotonergic drugs or in overdose.
Most severe serotonin syndrome cases involve an MAOI (including moclobemide) plus an SSRI.
Caution is advised when switching strategies involve combining serotonergic drugs.

Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition that can occur when there is too much serotonin in the body.
Serotonin is a neurotransmitter that plays a role in mood, sleep, appetite, and other functions.
Symptoms of serotonin syndrome can vary depending on the severity of the condition.

Mild Serotonin Syndrome Symptoms

Insomnia
Anxiety
Nausea
Diarrhea
Hypertension
Tachycardia
Hyper-reflexia (increased reflexes)

Moderate Serotonin Syndrome Symptoms

Agitation
Myoclonus (muscle twitching)
Tremor
Mydriasis (pupil dilation)
Flushing
Diaphoresis (sweating)
Low fever

Antidepressant Discontinuation Symptoms

Antidepressants, like many medications, can cause withdrawal symptoms when discontinued.
"Discontinuation symptoms" and "withdrawal" differ semantically, with "withdrawal" suggesting addiction.
While antidepressants aren't addictive, this distinction may be irrelevant for patients experiencing symptoms.
"Receptor rebound" explains withdrawal symptoms – for example, drugs with anticholinergic side effects may cause diarrhea upon discontinuation.
Symptoms can be entirely new or similar to pre-medication illness symptoms.
Rapid onset (days, within 3-5 drug half-lives), rapid response to reintroduction, and distinct somatic/psychological symptoms distinguish withdrawal from relapse.
SSRIs and related drugs (SNRIs, other serotonin reuptake inhibitors) are associated with various withdrawal symptoms.

SSRI Withdrawal Syndrome Symptoms

SSRI withdrawal syndrome can cause a variety of symptoms, categorized into sensory, affective, sleep disturbance, gastrointestinal, sexual, general somatic, disequilibrium, and cognitive.
Sensory symptoms include paresthesia, numbness, "shock-like" sensations, rushing noises, visual trails, hyperacusis, and unusual sensory experiences.
Affective symptoms include irritability, anxiety, low mood, tearfulness, dread, and panic attacks.
Sleep disturbances include insomnia, nightmares, and excessive dreaming.
Gastrointestinal symptoms include nausea, vomiting, diarrhea, and anorexia.
Sexual symptoms include genital hypersensitivity and premature ejaculation.
General somatic symptoms include flu-like symptoms, lethargy, headache, tremor, sweating, weakness, tachycardia, muscle aches, and shaking.
Disequilibrium symptoms include dizziness, light-headedness, vertigo, ataxia, and gait instability.
Cognitive symptoms include confusion, decreased concentration, amnesia, depersonalization, and derealization.

Pharmacological Factors

Drug Half-Life: Directly correlates with the severity and onset of withdrawal symptoms. Shorter half-life drugs, such as venlafaxine and paroxetine, are associated with more severe withdrawal symptoms.
Other Pharmacokinetic factors: Non-linear pharmacokinetics can also influence withdrawal symptoms.

Pharmacodynamics

Receptor Affinities: Antidepressants with a higher affinity for the serotonin transporter are potentially linked to a greater risk of withdrawal symptoms.

Treatment Factors

Duration of Treatment: The length of antidepressant use can influence withdrawal symptom severity.
Dose: Higher doses may be associated with more significant withdrawal reactions.
Method of Tapering: A gradual reduction in dosage, known as tapering, can help minimize withdrawal risks.

Patient Specific Factors

Prior Experience and Anticipation Effects: Previous experience with antidepressant withdrawal and anticipatory anxiety can influence the severity of withdrawal symptoms.

Incidence and Severity

Antidepressant discontinuation symptoms are common, affecting a significant portion of patients.
Studies report a wide range of incidence rates, from 27% to 86%, with an average of 56%.
Fluoxetine withdrawal symptoms are reported in 9% to 77% of cases.
Paroxetine withdrawal symptoms are reported in 42% to 100% of cases.
Almost all antidepressants, except possibly agomelatine, are associated with withdrawal symptoms.

Time Course

The timing and severity of symptoms are related to the half-life of the antidepressant.
Short half-life drugs like paroxetine and venlafaxine cause symptoms quickly, within a day or two.
Fluoxetine withdrawal symptoms may be delayed, appearing 2 to 6 weeks after discontinuation.
Symptoms can vary significantly in duration, intensity, and combination.
While some symptoms are mild and resolve on their own, others can be prolonged and severe.
Symptom severity may be amplified by the lack of warning about potential withdrawal effects.
Specific drugs are associated with particular symptoms (refer to Table 3.9 for further details).
The Discontinuation–Emergent Signs and Symptoms (DESS) scale can be used to quantify and assess symptom severity.

Agomelatine

Reported to have a low risk of discontinuation symptoms.
Uncommon side effects include anxiety, headache, insomnia, irritability, and muscle pain.
A single case report of acute dystonia has been documented.

Bupropion

Uncommon, but some cases have described anxiety, headache, insomnia, irritability, and muscle pain.
A single case report of acute dystonia has been documented.

MAOIs

Common side effects include agitation, irritability, lack of coordination, movement disorders, insomnia, sleepiness, vivid dreams, difficulty thinking, slow speech, and rapid speech.
Occasionally, hallucinations and paranoid delusions are reported.
Flu-like symptoms are reported with moclobemide (a reversible inhibitor of monoamine oxidase –RIMA).

NaSSAs

Panic attacks, anxiety, restlessness, irritability, mild mania, insomnia, dizziness, numbness or tingling, nausea, and vomiting are possible side effects.

Serotonin Modulators

No reported discontinuation symptoms, but these are relatively new drugs with limited clinical experience.
Shared pharmacological properties with SSRIs suggest the possibility of withdrawal symptoms.

TCAs

Common side effects include general physical discomfort, gastrointestinal distress, sleep disturbances, restlessness, Parkinsonian symptoms, mild mania or mania, and irregular heartbeat.

Trazodone

Possible side effects include mild mania, anxiety, restless sleep, nightmares, feeling detached from reality, formication (sensation of insects crawling on the skin), and headaches.

Antidepressant Discontinuation Syndrome

Symptoms can be mistaken for a relapse of illness or a new physical illness.
Symptoms can be severe enough to interfere with daily functioning.
Patients may believe that antidepressants are addictive and refuse treatment due to discontinuation symptoms.
Discontinuation with paroxetine has been linked to emergent suicidal thoughts.

Risk Factors

Short half-life drugs (e.g., paroxetine, venlafaxine) increase the risk of discontinuation symptoms, especially with inconsistent dosing.
Longer duration of antidepressant use (8 weeks or more) increases the risk.
Higher doses of antidepressants are associated with increased risk.
Anxiety symptoms at the start of antidepressant therapy, particularly with SSRIs, raise the risk.
Other centrally acting medications (e.g., antihypertensives, antihistamines, antipsychotics) can increase the risk.
Children and adolescents are at higher risk for discontinuation symptoms.
Younger patients are also more vulnerable.
Previous experience with withdrawal symptoms increases the risk.
Neonates born to mothers taking antidepressants are at risk for withdrawal symptoms.

Avoiding Discontinuation Symptoms

Gradual discontinuation of antidepressant therapy is recommended.
The shorter the drug's half-life, the slower the taper should be.
Slower taper may be necessary near the end of the withdrawal process.
MAOIs require prolonged tapering periods.
Transitional period for other medications like agomelatine may not be necessary, but slow withdrawal is generally recommended.
Hyperbolic tapering may be necessary to minimize symptoms.

Treating Discontinuation Symptoms

Treatment is primarily pragmatic.
Mild symptoms can be reassured as common and temporary (days or weeks).
Severe symptoms necessitate reintroduction of the original antidepressant or a similar drug with a longer half-life, followed by a gradual taper.
Anticholinergic agents may be helpful in tricyclic withdrawal.
Fluoxetine has been shown to be effective for symptoms associated with stopping paroxetine, sertraline, clomipramine, or venlafaxine.
Benzodiazepines may be used for short-term management of anxiety and insomnia.

Key Points for Patients

Antidepressants are not addictive in the medical sense.
Discontinuation symptoms are common and should be anticipated.
Stopping antidepressants abruptly increases the risk of withdrawal symptoms and relapse.
Missed or late doses can trigger discontinuation symptoms.
Pre-dose discontinuation symptoms can lead to an earlier need for medication.

Sertraline Dose and SERT Occupancy

Panel (a) of Figure 3.4 shows a sigmoid curve demonstrating a linear relationship between Sertraline dose reduction and its effect on receptor targets.
As the Sertraline dose decreases, its effect on SERT occupancy increases, but the rate of increase is greater with smaller dose reductions.
Panel (b) of Figure 3.4 shows a hyperbolic curve, indicating that even small reductions in the effect on receptor targets require a large decrease in Sertraline dose.
Key takeaway: Both panels highlight the non-linear relationship between Sertraline dose and SERT occupancy.
Panel (a) shows a linear relationship between dose reduction and effect reduction.
Panel (b) reveals a hyperbolic relationship, emphasizing that the final dose before Sertraline discontinuation needs to be very low to minimize withdrawal effects.

Antidepressant Tapering

Patients must be informed about the risk of withdrawal symptoms when stopping any antidepressant. Some drugs, such as paroxetine and venlafaxine, are more likely to cause severe withdrawal.
Abruptly stopping antidepressants is the most common cause of severe and long-lasting withdrawal symptoms and relapse.
Gradual and careful tapering can minimize withdrawal symptoms.
Most patients take approximately 3 months to taper off medication, but some may take up to 2 years.
Past experiences with stopping antidepressants can be informative for predicting withdrawal symptoms.
Non-pharmacological coping skills can be helpful in preparing for antidepressant tapering.
Mindfulness-based cognitive therapy (MB-CT) has evidence supporting its use in stopping antidepressants.
Withdrawal symptoms do not necessarily indicate the need for a full dose of medication, but may indicate a need to slow the tapering rate.
For low-risk patients, a test reduction of 5-10% is recommended.
Withdrawal symptoms should be monitored for 2-4 weeks.
If initial reduction was tolerable, continue reducing the dose at the same proportion.
If symptoms are intolerable, the taper should proceed at a slower pace.
If withdrawal symptoms become intolerable, hold the current dose, or increase to the last tolerable dose until symptoms resolve.
Tapering may need to be very gradual, with smaller reductions and longer periods between reductions.
Distressing withdrawal symptoms do not mean a patient cannot stop antidepressants, but that they need to taper more slowly.
Fluoxetine withdrawal symptoms can be delayed due to its long half-life.
Fluoxetine dose can be reduced by decreasing dosing frequency.
Liquid formulations of antidepressants can facilitate tapering.
Final doses before stopping medication may need to be very small to minimize effects on transmitter systems.

Electroconvulsive Therapy (ECT) & Psychotropic Medications

Psychotropic medications are often continued during ECT, and some antidepressants may enhance ECT efficacy.
Different psychotropic drugs have varying effects on seizure duration during ECT.
Choice of anesthetic agent significantly affects seizure duration and ECT efficacy.
Factors influencing seizure threshold and duration include concurrent medications and patient characteristics.
ECT frequently causes confusion and disorientation; more rarely, it causes delirium.
Concurrent lithium may increase the risk of delirium.
Two case reports suggest a potential association between ECT and serotonin syndrome, especially with certain medication combinations.
Limited evidence supports the use of thiamine to reduce post-ECT confusion.
Nortriptyline may enhance ECT efficacy and reduce cognitive adverse effects.
Cognitive enhancers (donepezil, memantine, rivastigmine) might improve cognitive function and reduce ECT-induced cognitive side effects.
Ibuprofen can be used to prevent headache, and intranasal sumatriptan can treat headaches.

Tapering Antidepressants

Patients should be warned of potential withdrawal symptoms when stopping antidepressants.
Paroxetine and venlafaxine are commonly associated with severe withdrawal symptoms.
Abrupt discontinuation of antidepressants is thought to be the most likely cause of severe and long-lasting withdrawal symptoms and relapse.
Gradual tapering can manage withdrawal symptoms at tolerable levels.
Most patients take around 3 months to taper off, some up to 2 years.
Past experiences of stopping antidepressants can inform expectations and predict potential symptoms.
Consider providing support during tapering, such as work adjustments, family support, and non-pharmacological coping skills.
Mindfulness-based cognitive therapy (MB-CT) may be helpful during tapering.
Negative psychological and physical symptoms during withdrawal do not necessarily indicate a need for the full dose of the drug; it might just mean the taper rate needs to be slowed.
Be familiar with the wide variety of withdrawal symptoms to mitigate anxiety.

Tapering Process: Risk Stratification

Low-risk patients:
- 6 months of use, short half-life antidepressant, past history of withdrawal symptoms
- Recommend a test reduction of 5-10%
- Monitor withdrawal symptoms for 2-4 weeks, or until symptoms resolve.
- Use daily symptom ratings or standardized measures like the DESS (Discontinuation-Emergent Signs and Symptoms scale).
- Titrate further reductions based on tolerability.
- Continue reducing at the same proportion and rate if initial reduction was tolerable.
- If symptoms were intolerable, slow down the taper rate or re-instate the previous dose.

Tapering: Troubleshooting

If withdrawal symptoms become intolerable:
- Hold the current dose for longer to allow them to resolve.
- If symptoms are very unpleasant, increase the dose to the last tolerable level and hold it until symptoms resolve.
- After stabilization, taper more gradually with smaller reductions and longer periods between reductions.
Some patients can only reduce by 5% of the last dose per month.
Distressing withdrawal symptoms do not mean the patient cannot stop antidepressants, just that they need to taper more slowly.

Tapering Fluoxetine

Fluoxetine's long half-life can delay withdrawal symptoms by weeks, requiring careful attention
Larger reductions in fluoxetine may be relatively tolerable due to the extended withdrawal period.
Reduce fluoxetine dose by decreasing the frequency of dosing (e.g., 6 days a week to 5 days a week, and so on).

Practical Considerations

Current tablet formulations do not allow for pharmacologically informed tapering regimens; liquid formulations or Dutch tapering strips are needed.
If liquid formulations are not available, they may need to be compounded or patients can be switched to medications with liquid formulations.
Final doses before stopping the drug may need to be very small (e.g., less than 1mg for sertraline).

Electroconvulsive Therapy (ECT) and Psychotropic Drugs

Psychotropic drugs are often continued during ECT, and some enhance its efficacy.
There are few well-controlled studies on the effects of psychotropic drugs on ECT, so recommendations should be viewed with caution.
Antidepressants can enhance ECT efficacy.
Choice of anesthetic significantly impacts seizure duration, post-ictal confusion, and ECT efficacy.
Concurrent Lithium may increase the risk of delirium after ECT.
Serotonin Syndrome has been reported in two case reports during ECT. Close observation is essential.
Thiamine (200mg daily) may reduce post-ECT confusion.
Nortriptyline enhances ECT efficacy and reduces cognitive adverse effects.
Cognitive enhancers (donepezil, memantine, rivastigmine) might improve cognitive function and reduce ECT-induced cognitive side effects.
Ibuprofen may prevent headaches, and intranasal sumatriptan can treat them.

Effect of Psychotropic Drugs on Seizure Duration in ECT

Benzodiazepines: Reduce seizure duration during ECT, but generally should be avoided as they may raise the seizure threshold and complicate anesthesia
- Long-acting benzodiazepines may need to be discontinued several days before ECT
- If sedation is required, consider hydroxyzine instead
- If benzodiazepine use is essential and long-term, continue use with higher stimulus bilaterally
SSRIs: Minimal effect on seizure duration, generally considered safe to use during ECT
- Be cautious of possible complex pharmacokinetic interactions with anesthetic agents
- Isolated case reports of serotonin syndrome with fluoxetine and paroxetine during ECT
Venlafaxine: Minimal effect at standard doses, but potential for increased risk of asystole at doses above 300mg/day
- Limited data available
- ECG recommended especially with higher doses
Mirtazapine: Minimal effect, small increase in seizure duration possible
- Appears safe to use during ECT
- May enhance ECT efficacy and reduce post-ECT nausea and headache
Duloxetine: Unknown effect on seizure duration
- Limited data; one case report suggests no complication with ECT, another reports possible link to ventricular tachycardia
TCAs: Possibly increased seizure duration, few relevant data but many TCAs lower seizure threshold
- Associated with arrhythmia following ECT, should be avoided in elderly and those with cardiac disease
- It may be preferable to continue TCA treatment during ECT with close monitoring
- Beware of hypotension and prolonged seizure risk
MAOIs: Minimal effect on seizure duration, very limited relevant data, but long history of ECT use during MAOI therapy
- MAOIs likely do not affect seizure duration
- Possible interactions with sympathomimetics used in anesthesia leading to hypertensive crisis
- Transdermal selegiline seems safe
- Continue MAOI treatment during ECT, inform the anesthetist, monitor for hypotension
Note:* Individual responses may vary.

Lithium and ECT

Lithium may increase ECT seizure duration but conflicting data exists.
Combining lithium and ECT might increase delirium and confusion.
Some experts advise stopping lithium 48 hours prior to ECT.
In the UK, ECT is frequently used during lithium therapy, but with close monitoring and low stimulus initiation.
Lithium potentiates the effects of non-depolarizing neuromuscular blockers.
Concurrent use of thiopentone or propofol with lithium decreases seizure threshold.

Antipsychotics and ECT

Effect on seizure duration is variable.
Phenothiazines and clozapine may prolong seizures, and withdrawal before ECT is suggested by some.
Safe concurrent use has been reported, particularly with clozapine.
ECT is effective even for clozapine non-responders.
Aripiprazole, quetiapine, and ziprasidone appear safe but limited data exists.
One case series suggests antipsychotics may increase post-ictal cognitive dysfunction.

Antiseizure Medications and ECT

If used for mood stabilization, continue but prepare for higher energy stimulus.
For epilepsy, antiseizure medications normalize seizure threshold.
Interactions are possible; valproate may prolong thiopental effects, and carbamazepine may inhibit neuromuscular blockade.
A study found no significant differences in seizure duration, threshold, or cognition between carbamazepine and valproate.
Lamotrigine reportedly causes no problems.

Barbiturates and ECT

All barbiturates reduce seizure duration during ECT.
Thiopental and methohexital may cause cardiac arrhythmia.

Psychostimulants in Depression

Psychostimulants can reduce fatigue, promote wakefulness, and elevate mood.
Amfetamines have been used to treat depression since the 1930s.
Modafinil is a newer psychostimulant evaluated as an adjunct to antidepressants.
Amfetamines are rarely used for depression due to tolerance, dependence, and potential for paranoid psychosis with prolonged high doses.
Methylphenidate is more widely used but may have similar drawbacks to amfetamines.
Modafinil does not seem to induce tolerance, dependence, or psychosis but lacks the euphoric effects of amfetamines.
Armodafinil, a longer-acting version of modafinil, is available in some countries.
Psychostimulants differ from antidepressants in that their mood-elevating effects are rapid but short-lived.
Amfetamines and methylphenidate may be useful in situations requiring a quick effect and where dependence is not a concern, like depression associated with terminal illness.
Ketamine is also considered for prompt antidepressant effects.
Psychostimulants might be justified in severe, prolonged depression resistant to standard treatments.
Modafinil may be used as an adjunct to antidepressants in a broader range of patients and for hypersomnia and fatigue.
Research on psychostimulants in depression is insufficient, with data being poor and inconclusive.
Careful consideration is needed regarding the use of psychostimulants in depression due to unestablished short- and long-term safety.
The inclusion of specific drugs in the table is not a recommendation for their use.

Stimulants in Depression

Stimulants are explored as treatments for depression, both as monotherapy (sole treatment) and adjunctive therapy (used alongside other treatments).

Monotherapy for Uncomplicated Depression

Modafinil (100-200mg daily): Only case reports exist; efficacy not proven.
Methylphenidate (20-40mg daily): Minimal effectiveness reported.
Dexamphetamine (20mg daily): Minimal effectiveness reported.

Adjunctive Therapy to Accelerate or Improve Response

SSRI (Selective Serotonin Reuptake Inhibitor) + Methylphenidate (10-20mg daily): No clear effect on the time to response.
SSRI + Modafinil (400mg daily): Improved response observed compared to SSRI alone.
Tricyclic Antidepressant + Methylphenidate (5-15mg daily): Single open-label trial suggests faster response but requires further confirmation.
SSRI or SNRI (Serotonin-Norepinephrine Reuptake Inhibitor) + Lisdexamfetamine (20-70mg daily): No superiority over placebo.

Recommendations

Monotherapy: Standard antidepressants are the preferred treatment option. Psychostimulants are not recommended for monotherapy.
Adjunctive Therapy: While meta-analysis suggests adjunctive therapy might be helpful, psychostimulants generally are not recommended. Modafinil, however, may be a potential option.

Adjunctive Treatments for Depression

Modafinil and Methylphenidate can be used adjunctively for depression with fatigue and hypersomnia.
Modafinil may induce suicidal ideation.
Methylphenidate has shown benefits for fatigue in hospice patients.
Combining stimulants with antidepressants may be beneficial.
One study suggests Methylphenidate may reduce self-harm and suicide attempts.
A large case series of 50 patients showed an improvement in symptoms using Methylphenidate or Dexamfetamine.
Lisdexamfetamine had a small, non-significant effect on depressive symptoms when compared to placebo.

Adjunctive Treatments for Bipolar Depression

Modafinil, Armodafinil, and Methylphenidate can be used as adjunctive treatments for bipolar depression.
Modafinil and Armodafinil have shown significant benefits over placebo in treating bipolar depression.
Lisdexamfetamine also shows promise as an adjunctive treatment, improving symptoms over placebo.
Studies suggest stimulants are generally well-tolerated and effective in treating bipolar depression.
There is no evidence of treatment-emergent mania with stimulants.

Monotherapy and Combination Therapies for Various Conditions

Methylphenidate and dexamfetamine are potential treatments for late-stage terminal cancer, showing positive effects on mood, fatigue, and pain.
Limited evidence supports the use of methylphenidate for depression in the elderly, but effectiveness is seen in some controlled studies.
A combination of methylphenidate and citalopram may be faster acting than monotherapy treatments for depression in the elderly.
Methylphenidate is a potential option for post-stroke depression but requires further research.
Standard antidepressants are preferred for depression secondary to medical illness, as there is insufficient data on psychostimulants.
Dexamfetamine may aid in treating depression and fatigue associated with HIV.
Methylphenidate potentially outperforms antidepressants for depression in patients with traumatic brain injury, but more research is needed.

Post-Stroke Depression

Depression is common in stroke survivors (30-40%), hindering recovery.
Antidepressants can improve recovery, cognition, motor function and reduce mortality.
Prophylaxis is a consideration due to high incidence of post-stroke depression.
Antidepressants like Nortriptyline, fluoxetine, escitalopram, duloxetine, and sertraline can prevent post-stroke depression.
Mirtazapine may both prevent and treat depression.
A large study suggests Mirtazapine (and Venlafaxine) may increase the risk of stroke compared to SSRIs or TCAs.
Routine use of antidepressants for post-stroke depression prevention is not recommended due to limited evidence.
Three recent studies showed the risks of fluoxetine outweigh benefits in reducing depression.
Complications in treatment include medical comorbidities and potential drug interactions, especially with warfarin.
Fluoxetine, citalopram, and nortriptyline are widely studied and effective.
SSRIs and nortriptyline are recommended for post-stroke depression.
Concerns remain regarding SSRIs and stroke risk, although evidence suggests they may protect against embolic stroke but potentially increase the risk of hemorrhagic stroke.
Despite these concerns, antidepressants remain effective treatment for post-stroke depression.
Inadequate treatment of depression increases stroke risk.
Paroxetine may be the drug of choice for post-stroke depression, although the data is limited.
A large meta-analysis ranked Mirtazapine first for response rate followed by Venlafaxine and Escitalopram for Chinese patients.
Caution is required with SSRIs in hemorrhagic stroke due to potential risk of increasing hemorrhagic stroke, especially with warfarin or anti-platelet drugs.
Citalopram or Escitalopram may be preferred for patients taking warfarin due to lower interaction potential.
Where SSRIs are used with anticoagulants or aspirin, a proton-pump inhibitor might be prescribed for gastric protection.
Nortriptyline is an alternative that doesn’t appear to increase bleeding risk.

Alternative Routes of Antidepressant Administration

Non-oral Administration: Used when oral ingestion is difficult or contraindicated.
Limited Formulations: Few non-oral formulations commercially available and may require special manufacturing.
Accountability: Prescribers bear accountability for adverse effects of non-oral medications.
Alternative Psychotropics: Some atypical antipsychotics may have antidepressant properties and are available in non-oral forms.

Sublingual Administration

Case reports: Show effectiveness of sublingual fluoxetine liquid in medically compromised patients.
Dosing: Doses up to 60mg daily achieved lower end of therapeutic range for fluoxetine and norfluoxetine.
Ketamine: Sublingual ketamine demonstrates potential efficacy and better tolerability compared to other routes.

Buccal Administration

Selegiline: Available as oral lyophilisates for buccal absorption but lacks antidepressant activity at licensed doses.
Doxepin: Under development for buccal-adhesive delivery system but no commercial product available.
Amitriptyline: Buccal administration in a case report showed therapeutic plasma levels.
Mirtazapine: Orodisspersible mirtazapine assumed to absorb buccally but lacks evidence of actual absorption.

Intravenous and Intramuscular Injections

Intravenous: Avoids first-pass effect, potentially leading to higher plasma levels and greater response but not necessarily faster onset of action.
Citalopram: Intravenous followed by oral maintenance therapy may be beneficial for severely depressed hospitalized patients.
Mirtazapine: Available intravenously and well-tolerated in depressed patients.
Amitriptyline: Previously available intravenously and intramuscularly, used for post-operative pain and depression but rarely available now.
Clomipramine: Widely studied intravenously; pulse-loading doses show rapid decrease in obsessive compulsive disorder symptoms.
Allopregnanolone (brexanolone): Licensed for intravenous treatment of postpartum depression, not suitable for other types of depression.
Ketamine: Intravenous administration demonstrates rapid but short-lived antidepressant effects.
Scopolamine (hyoscine): Intravenous administration shows rapid antidepressant effects in unipolar and bipolar depression.

Transdermal Administration

Amitriptyline gel: Used for chronic pain management but no published data on plasma levels achieved transdermally.
Nortriptyline: Formulated as a transdermal patch for smoking cessation but not studied for depression.
Selegiline: Transdermal selegiline provides sustained plasma concentration, bypassing first-pass metabolism and may not require tyramine restriction at lower doses.

Rectal Administration

Limited availability: No readily available antidepressant suppositories, but extemporaneous preparation possible.
Amitriptyline: Rectal suppositories prepared extemporaneously showed subjective success.
Doxepin: Rectal administration in cancer-related pain achieved therapeutic plasma levels.
Imipramine and Clomipramine: Extemporaneously manufactured suppositories showed comparable plasma levels to oral administration.
Trazodone: Successfully administered rectally post-operatively.
Sertraline: Tablets administered rectally with success in a critically ill patient.

Intranasal Administration

Esketamine: Available as a nasal spray licensed for treatment-resistant major depressive disorder.
Administration: Specific practices required for nasal spray application may not be feasible in medically unwell patients.
**UK NICE: ** Not recommended for treatment-resistant depression due to concerns over cost-effectiveness and clinical effectiveness for long-term use.

Antidepressant Prophylaxis

First Episode Treatment:
- Treat for 6-9 months after full remission.
- 50% experience relapse within 3-6 months if treatment is stopped immediately.
- Longer treatment periods (50 weeks) have lower relapse rates than shorter periods.
- Non-continuous use of antidepressants during the first 6 months of treatment predicts higher relapse rates.
Recurrent Depression:
- 15% of cases are unremitting, and 35% are recurrent.
- 50% of patients with a first-onset episode recover fully.
- Factors increasing the risk of recurrence:
  - Family history of depression
  - Recurrent dysthymia
  - Concurrent non-affective psychiatric illness
  - Female gender
  - Long episode duration
  - Degree of treatment resistance
  - Chronic medical illness
  - Social factors (e.g., lack of confiding relationships and psychosocial stressors).

Prophylactic Treatment Efficacy

Reduces relapse risk by approximately two-thirds.
Benefits persist for 36 months and beyond.
Effect size is similar across diverse groups (first episode, multiple episode, and chronic).
Studies in first-episode patients are needed to confirm long-term benefits.
Maintenance treatment is beneficial for elderly patients, including those with first-episode depression.
A small RCT showed benefit from prophylactic antidepressants in adolescents.
Many patients who could benefit from maintenance treatment do not receive it.
Assuring optimal management of long-term depression dramatically reduces mortality.

Concerns and Alternatives

Confounding factors in maintenance trials:
- Abrupt withdrawal might amplify the risk of relapse.
- Improved treatment with active drugs might skew results.
Possible long-term risks of antidepressants:
- Increased risk of GI and cerebral haemorrhage.
- Increased risk of interaction with other drugs causing bleeding or hyponatremia.
Maintenance treatment should only be continued if there is clear evidence of efficacy.
Residual symptoms predict poor outcomes and a higher risk of relapse.
ECT relapse rates similar to those after stopping antidepressants.
Prophylactic treatment ideally uses a different drug than the one that failed in the first instance.
Lithium may be helpful for prophylaxis, but its relative efficacy to antidepressants is unknown.
NICE recommends lithium should not be the sole prophylactic drug.
Maintenance treatment with lithium protects against suicide.
Combination therapies with lithium and nortriptyline have some support.

Patient Information

A single episode of depression should be treated for 6-9 months after remission.
The risk of recurrence increases with each episode.
Those with multiple episodes might require treatment for many years.
Antidepressants significantly increase the chances of staying well.
Antidepressants are:
- Effective
- Not addictive (although withdrawal symptoms are expected)
- Do not lose efficacy over time
- Have no known long-term side effects.
Medication needs to be continued at the treatment dose.
Alternatives may be possible if side effects are intolerable.
Stopping medication abruptly can cause unpleasant discontinuation effects and increase relapse risk.
Gradual medication reduction under supervision is essential when discontinuing.

Drug Interactions with Antidepressants

Two main types of interactions:
- Pharmacokinetic: One drug alters the absorption, distribution, metabolism, or elimination of another.
- Pharmacodynamic: One drug alters the effects of another through direct competition at receptor sites, augmentation of neurotransmitter pathways, or effects on organ functioning.

Pharmacokinetic Interactions

CYP450 Enzymes: The most common pharmacokinetic interaction involves drugs that inhibit or induce CYP450 enzymes.
Clinical Consequences: Difficult to predict for each patient. Some interactions can be highly significant: e.g., paroxetine (CYP2D6 inhibitor) with tamoxifen can increase the risk of death in breast cancer patients.
Factors Influencing Interactions: The degree of enzyme inhibition/induction, pharmacokinetic properties of the affected drug, relationship between plasma level and effect, and patient-specific factors like metabolism variability and co-morbid illnesses.

Pharmacodynamic Interactions

Tricyclic Antidepressants (TCAs):
- H1 Blockers: Can exacerbate sedation effects when combined with other sedatives or alcohol.
- Anticholinergic: Can worsen dry mouth, blurred vision, and constipation when combined with other anticholinergic agents.
- α1-Blockers: Can worsen postural hypotension when combined with other α1-blockers or antihypertensives.
- Arrhythmogenic: Caution needed when combined with drugs affecting cardiac conduction.
- Lower Seizure Threshold: Caution needed when combined with other proconvulsive drugs (antipsychotics).
- Serotonin Reuptake Inhibition: Risk of serotonin syndrome when combined with other serotonergic drugs (tramadol, SSRIs, MAOIs, triptans).
SSRIs/SNRIs:
- Increased Serotonin: Main concern is serotonin syndrome when co-prescribed with other serotonergic drugs.
- Platelet Aggregation Inhibition: Increased risk of bleeding, especially when combined with aspirin and NSAIDs.
- Hyponatraemia: May exacerbate electrolyte disturbances caused by diuretics.
- Osteopenia: May worsen bone mineral density issues caused by prolactin-elevating drugs.
MAOIs:
- Monoamine Inhibition: Potentially fatal serotonin syndrome when co-prescribed with serotonergic drugs.
- Sympathomimetic Interactions: Can cause hypertensive crises when combined with sympathomimetic drugs that raise blood pressure.
- Tyramine Interactions: Can cause hypertensive reactions when combined with foods containing high tyramine levels (aged & fermented).

Reducing Interaction Risks

Polypharmacy: Select safer drugs for combination therapy and monitor side effects closely when adding a second antidepressant.
Similar Pharmacology: Avoid co-prescription of drugs with similar pharmacology but not marketed as antidepressants (atomoxetine, bupropion).

Cytochrome P450 Enzymes and Drug Interactions

CYP enzymes are a family of enzymes that play a crucial role in drug metabolism, primarily in the liver.
Genetic polymorphism in CYP enzymes can lead to variations in drug metabolism, influencing drug efficacy and potential adverse effects.
Some individuals are poor metabolizers due to genetic factors, affecting how they process certain medications.
CYP enzyme induction leads to increased metabolism of certain drugs, potentially reducing their effectiveness.
CYP enzyme inhibition can result in decreased drug metabolism, potentially leading to increased drug levels and adverse effects.

CYP Enzyme Induction

Carbamazepine induces CYP1A2, CYP2B6, CYP2C9, CYP2D6, and CYP3A4/5/7.
Rifampicin induces CYP2B6, CYP2C9, CYP2D6, and CYP3A4/5/7.
Phenytoin induces CYP1A2, CYP2C9, and CYP2D6.
Prednisolone induces CYP2D6 and CYP3A4/5/7.

CYP Enzyme Inhibition

Cimetidine inhibits CYP1A2, CYP2C9, and CYP2C19.
Fluvoxamine inhibits CYP1A2, CYP2C9, and CYP3A4/5/7.
Erythromycin inhibits CYP1A2 and CYP3A4/5/7
Ketoconazole inhibits CYP3A4/5/7.
Grapefruit juice inhibits CYP3A4/5/7.

### CYP Enzyme Substrates

The table includes a list of drugs that are metabolized by the different CYP enzymes, providing insights into potential drug interactions.

Cardiac Effects of Antidepressants

Agomelatine does not appear to have significant effects on heart rate, blood pressure, or QT interval. However, a single case of QTc prolongation has been reported. It is cautiously recommended for use.
Bupropion can slightly increase heart rate and blood pressure, with the potential for significant increases in blood pressure in some cases. Although it typically shortens the QTc interval, prolongation has been reported in overdoses. It is well tolerated for smoking cessation in post-MI patients.
Citalopram and Escitalopram are associated with a small decrease in heart rate and blood pressure, but they may increase the QTc interval in a dose-dependent manner. Torsades de Pointes has been reported, primarily in overdoses. Caution is advised for patients with recent MI or uncompensated heart failure, but there is evidence suggesting safety in individuals with cardiovascular disease.
Duloxetine can slightly increase heart rate and blood pressure, with significant effects noted in its Summary of Product Characteristics (SPC). It is not recommended in patients with cardiac disease due to potential complications from increased heart rate or blood pressure.
Fluoxetine can cause a small decrease in mean heart rate but has minimal effects on blood pressure. It does not impact the QTc interval. It is generally considered safe for use in patients with acute MI or uncompensated heart failure.
Fluvoxamine has minimal effects on heart rate and blood pressure, with no significant impact on QTc interval. It is used with caution, as limited changes in ECG have been observed.

Drug Effects on Heart Rate

Levomilnacipran, Milnacipran, and Reboxetine can increase heart rate slightly.
Lofepramine can moderately increase heart rate.
MAOIs can decrease heart rate.
Mirtazapine and Paroxetine have minimal effects on heart rate.
Moclobemide can marginally decrease heart rate.

Drug Effects on Blood Pressure

Levomilnacipran and Milnacipran can slightly increase blood pressure.
Lofepramine can decrease postural blood pressure compared to other tricyclic antidepressants.
MAOIs can cause postural hypotension and a risk of hypertensive crisis.
Mirtazapine and Paroxetine have minimal effects on blood pressure.
Moclobemide has minimal effects on blood pressure, but isolated cases of hypertensive episodes have been reported.
Reboxetine can marginally increase both systolic and diastolic blood pressure but can cause postural decrease at higher doses.

Drug Effects on QT Interval

Levomilnacipran and Milnacipran have no effect on the QT interval.
Lofepramine can prolong the QT interval at higher doses.
MAOIs may shorten the QT interval, but this is unclear.
Mirtazapine, Paroxetine, and Moclobemide have no effect on the QT interval at normal doses.
Reboxetine has no effect on the QT interval.

Drug Effects on Arrhythmias and Conduction Disturbances

Levomilnacipran should be used with caution in patients with pre-existing tachyarrhythmias.
Lofepramine may cause arrhythmias at higher doses.
MAOIs can cause arrhythmias and decrease left ventricular function.
Milnacipran has no known effects on arrhythmias.
Reboxetine can cause atrial and ventricular ectopic beats, especially in the elderly.

Drug Effects on Myocardial Infarction

Levomilnacipran and Milnacipran should be used with caution in patients with cardiac issues.
Lofepramine is contraindicated in patients with recent MI.
MAOIs are not recommended for patients with cardiovascular disease.
Mirtazapine appears safe for post-MI patients.
Moclobemide should be used with general caution in patients with a history of cardiac disorders.
Paroxetine is probably safe for post-MI patients.
Reboxetine should be avoided in patients with coronary disease.

Additional Notes

TCAs refer to tricyclic antidepressants.
SSRIs refer to Selective Serotonin Reuptake Inhibitors.
CI refers to Contraindication.
LVF refers to Left Ventricular Failure.
BP refers to Blood Pressure.

Effects of Drugs on the Cardiovascular System

Sertraline: has minimal effect on heart rate and blood pressure at standard doses. It does not significantly affect the QTc interval.
Amiodarone: can cause bradycardia (slow heart rate), and hypotension (low blood pressure). It is known for prolonging the QTc interval, increasing the risk of arrhythmias, and potentially inducing conduction disturbances. Its use in the post-MI setting is limited.
Dofetilide: prolongs the QTc interval, increasing the risk of arrhythmias. This drug can induce conduction disturbances and is not recommended for use after a myocardial infarction (MI).
Flecainide: can cause bradycardia, hypotension, and prolonged QTc interval, increasing the risk of arrhythmias. It can also lead to conduction disturbances and is not indicated for post-MI use.
Procainamide: can cause bradycardia, hypotension, and prolonged QTc interval. While it can induce conduction disturbances, its use in the post-MI setting is limited.
Quinidine: can cause bradycardia, hypotension, prolonged QTc interval, and potentially induce arrhythmias. It is not recommended for use in the post-MI setting.
Sotalol: can cause bradycardia, hypotension, prolonged QTc interval, and potentially induce arrhythmias. It can also cause conduction disturbances and is not recommended for use in the post-MI setting.
Metoprolol: can decrease heart rate and blood pressure. It has minimal to no effect on the QTc interval and generally does not cause arrhythmias or conduction disturbances. It is commonly used in the post-MI setting.
Atenolol: can decrease heart rate and blood pressure. It has minimal to no effect on the QTc interval and generally does not cause arrhythmias or conduction disturbances. It is commonly used in the post-MI setting.
Bisoprolol: can decrease heart rate and blood pressure. It has minimal to no effect on the QTc interval and generally does not cause arrhythmias or conduction disturbances. It is commonly used in the post-MI setting.
Carvedilol: can decrease heart rate, blood pressure, and has minimal effect on the QTc interval. It is used in the post-MI setting.
Nifedipine: can reduce blood pressure and cause bradycardia. While it does not affect the QTc interval, it might cause conduction disturbances. Use is limited in the post-MI setting.
Diltiazem: can cause bradycardia, hypotension, and potentially prolong the QTc interval. It can induce conduction disturbances and is not commonly used in the post-MI setting.
Verapamil: can cause bradycardia, hypotension, and potentially prolong the QTc interval. It exhibits conduction disturbances and is not commonly used in the post-MI setting.
Digoxin: can cause bradycardia, and potentially induce arrhythmias. It is not recommended in the post-MI setting.
Theophylline: can increase heart rate. It does not significantly affect blood pressure or the QTc interval. It is not generally associated with arrhythmias or conduction disturbances.

SSRIs and Cardiac Disease

SSRIs are generally recommended in cardiac disease.
SSRIs may have anti-platelet activity, which can interact with cardiac medications.
Mirtazapine is a potential alternative to SSRIs, however, it is also associated with bleeding disorders.
SSRIs may protect against myocardial infarction.
Untreated depression worsens the prognosis of cardiovascular disease.
SSRIs and mirtazapine have neutral or beneficial effects on mortality post-MI.
Treatment of depression with SSRIs should not be withheld post-MI.
SSRIs may have anti-coagulant effects, which may contribute to their protective effects post-MI.
CBT may be ineffective in reducing the risk of mortality post-MI.
The anti-platelet effect of SSRIs can have adverse consequences.

Antidepressant-Induced Arrhythmia

Depression increases the risk of cardiovascular disease and sudden cardiac death, possibly due to factors like platelet activation, decreased heart rate variability, and reduced physical activity.
Tricyclic antidepressants (TCAs) are known to cause arrhythmias by blocking cardiac sodium channels and affecting potassium channels.
TCAs can cause ECG changes like prolonged PR, QRS, and QT intervals, and they can trigger Brugada syndrome.
Nortriptyline, a TCA, was linked to an increased risk of cardiac arrest in one study but not in a large cohort study.
Lofepramine, a TCA, has a unique profile, lacking overdose arrhythmogenicity, despite its metabolite, desipramine, being a potent potassium channel blocker.
Venlafaxine, a serotonin-norepinephrine reuptake inhibitor (SNRI), is a weak sodium channel antagonist and has a low risk of arrhythmia, even in massive overdoses.
SSRIs (selective serotonin reuptake inhibitors) like citalopram, escitalopram, sertraline, and others can prolong the QTc interval in overdose, but the clinical significance is uncertain.
Sertraline prolongs QT by 5-10 milliseconds at 400mg daily, but most SSRIs don't cause QT changes at therapeutic doses.
Citalopram and escitalopram have been linked to QT changes at standard doses, but large studies haven't found an increased risk of arrhythmia or death with these drugs at standard and higher doses.
Some antidepressants like vortioxetine, agomelatine, vilazodone, and levomilnacipran may have no effect on QT intervals.
Sertraline and mirtazapine (and to a lesser extent, citalopram, fluoxetine, and bupropion) have been found to be safe in patients at risk of arrhythmia due to recent myocardial infarction.
One trial found that SSRIs and trazodone decrease the risk of MI.
Citalopram has been reported to be safe in patients with coronary artery disease, but it's linked to a risk of torsades de pointes.
Escitalopram did not affect mortality in patients with heart failure.
Sertraline may help improve cardiovascular risk factors but older adults may have an increased risk of arrhythmia with all modern antidepressants.
Determining the relative cardiotoxicity of different antidepressants is challenging, and surveillance data show a link between marketed antidepressants and arrhythmia, although for many drugs, this may be coincidental.
The Fatal Toxicity Index (FTI) can be used as a measure to compare the toxicity of different medications.
Higher FTIs have been reported for TCAs, while SSRIs, mirtazapine, and reboxetine have lower FTIs.
The FTI does not solely reflect cardiotoxicity, as antidepressants can also cause serotonin syndrome, seizures, and coma.
Higher FTIs observed for some antidepressants, like venlafaxine, may reflect prescribing patterns rather than inherent toxicity.
Citalopram and escitalopram have very low overdose toxicity, despite QT prolongation seen in some overdoses.

Recommendations

TCAs (excluding lofepramine), venlafaxine, moclobemide, lofepramine, bupropion should be used with caution or avoided in individuals at risk of serious arrhythmia (history of heart failure, ventricular hypertrophy, previous arrhythmia, or MI).
An ECG should be performed at baseline and one week after each dose increase when using these medications in at-risk patients.
TCAs (except lofepramine) should be avoided in patients at risk of serious arrhythmia.
Perform ECG monitoring at baseline, one week after each dose increase, and periodically throughout TCA treatment for at-risk individuals.
The arrhythmogenic potential of TCAs and other antidepressants is dose-dependent.
Consider ECG monitoring for patients on higher licensed doses of antidepressants or those taking other drugs that might increase the risk of arrhythmia.

Hyponatremia Risk with Antidepressants

SSRIs and SNRIs have a high risk of hyponatremia, with strong supporting evidence.
Tricyclic antidepressants have a moderate risk of hyponatremia, with strong supporting evidence.
MAOIs have a low risk of hyponatremia, but the supporting evidence is weak.
NaSSas like mirtazapine and mianserin have a low risk of hyponatremia, with strong supporting evidence.
Bupropion has a low risk of hyponatremia, with moderate supporting evidence.
Agomelatine has a low risk of hyponatremia, with weak supporting evidence.

Hyponatremia and Antidepressants

Risk: All patients on antidepressants should be monitored for hyponatremia (low sodium levels in the blood).
Symptoms: Dizziness, nausea, lethargy, confusion, cramps, and seizures.
Highest Risk: The first 2-4 weeks after starting antidepressants.
Risk Reduction: Risk decreases over time, reaching baseline levels by 3-6 months.
Monitoring: Check serum sodium levels at baseline, 2 and 4 weeks, and then every 3 months for those at high risk.
High Risk Factors:
- Older age (especially women)
- Major surgery
- History of hyponatremia or low baseline sodium
- Co-therapy with other drugs known to cause hyponatremia (diuretics, NSAIDs, antipsychotics, carbamazepine, cancer chemotherapy, calcium antagonists, ACE inhibitors, and laxatives)
- Reduced renal function (GFR < 50 mL/min)
- Medical co-morbidity (hypothyroidism, diabetes, COPD, hypertension, head injury, CCF, CVA, various cancers)
- Low body weight
Treatment:
- Mild cases: Fluid restriction may be sufficient.
- Increasing sodium intake is suggested but impractical.
- If symptoms persist: Discontinue the antidepressant.
- Normal serum sodium: 136-145 mmol/L
- Serum sodium > 125 mmol/L: Monitor sodium daily until normal.
- Symptoms: Headache, nausea, vomiting, muscle cramps, restlessness, lethargy, confusion, and disorientation.
- Consider withdrawing the offending antidepressant.
- Serum sodium < 125 mmol/L: Urgent medical attention is required, as this is a more serious case of hyponatremia.

Prolactin Control

Prolactin release regulated by dopamine
Indirectly influenced by serotonin through 5HT1C and 5HT2 receptors

Antidepressants & Prolactin

Elevated prolactin levels (with or without symptoms) can occur with long-term antidepressant use
Prolactin increases are often small and transient
Symptoms are uncommon

SSRI and Hyperprolactinaemia

No association between SSRI use and breast cancer
Routine prolactin monitoring not recommended
Measure prolactin if symptoms of hyperprolactinaemia are suspected

Management

Consider switching to mirtazapine if symptomatic hyperprolactinaemia is confirmed
Switching to a different SSRI may also resolve symptoms

Antidepressant Impact on Prolactin

This table summarizes findings on how various antidepressant drugs affect prolactin levels, a hormone implicated in breast milk production.
The data is from two types of studies:
- Prospective studies: carefully planned research where participants are followed over time
- Case reports/series: individual reports or collections of cases detailing specific observations
Agomelatine: No evidence of prolactin changes in clinical trials. Melatonin itself is thought to reduce prolactin production.
Bupropion: Small doses (up to 100mg) don't appear to affect prolactin. May actually decrease prolactin levels.
MAOIs (Monoamine Oxidase Inhibitors): Mild changes in prolactin observed with phenelzine and tranylcypromine. Very rare reports of increased prolactin.
Mirtazapine: Strong evidence suggests no effect on prolactin. Rare reports of galactorrhea (breast milk production without pregnancy) and gynecomastia (breast enlargement in men).
SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors): A clear association exists between venlafaxine and duloxetine and elevated prolactin. Both drugs are linked to galactorrhea. Hyperprolactinemia (increased prolactin) linked to duloxetine has been treated with aripiprazole, an antipsychotic medication.
SSRIs (Selective Serotonin Reuptake Inhibitors): Prospective studies generally show no change in prolactin. Prescription monitoring suggests a slightly higher risk of non-puerperal lactation (breast milk production outside of pregnancy or breastfeeding) with SSRIs. A French study reported hyperprolactinemia in 1.6% of adverse event reports for SSRIs. Cases of galactorrhea have been reported with fluoxetine and paroxetine. Hyperprolactinemia, causing galactorrhea and amenorrhea (absence of menstrual periods), has been reported with escitalopram and fluvoxamine. Increased prolactin has been reported with sertraline.
Tricyclics: Some studies show small changes in prolactin levels, while others do not. Symptomatic hyperprolactinemia has been reported with imipramine, desipramine, and clomipramine. Galactorrhea has been reported with nortriptyline and when trazodone is added to citalopram. Increased prolactin may be linked to a positive response to amitriptyline.
Vortioxetine: No mention of prolactin changes in clinical trials. A review suggests a possible link between vortioxetine and galactorrhea.

Diabetes and Depression

There is an established link between diabetes and depression.
Prevalence of depression in diabetic patients ranges from 9 to 60%.
Diabetes doubles the odds of co-morbid depression.
Patients with depression and diabetes have a higher risk of cardiovascular problems and a 50% increased risk of mortality.
Depression negatively impacts metabolic control, and poor metabolic control can worsen depression.
Antidepressants are effective in treating depression in diabetic patients and may moderately improve glycaemic control.
Antidepressant use may be associated with reduced adherence to antidiabetic medication.

Treatment Recommendations

Screen all patients with depression for diabetes.
Use selective serotonin reuptake inhibitors (SSRIs) first-line, with data supporting sertraline, escitalopram and fluoxetine.
Serotonin-norepinephrine reuptake inhibitors (SNRIs) are likely safe, but data is limited.
Agomelatine shows promise with limited data.
Avoid tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) due to their effects on weight and glucose homeostasis.
Monitor blood glucose and HbA1c carefully when starting, changing, or discontinuing antidepressant treatment.

Effect of Antidepressants on Glucose Homeostasis and Weight

SSRIs generally have a favorable effect on diabetic parameters in patients with type II diabetes.
- They can decrease insulin requirements and improve HbA1c levels.
- Fluoxetine is associated with weight loss and enhanced insulin sensitivity.
- Sertraline may also reduce HbA1c.
- There is some evidence that long-term SSRIs may increase the risk of diabetes in general and gestational diabetes, but this is not conclusive.
TCAs are associated with increased appetite, weight gain, and hyperglycemia.
- Nortriptyline improved depression but worsened glycemic control in one study.
- Clomipramine has been reported to precipitate diabetes.
- Long-term use of TCAs seems to increase the risk of diabetes.
MAOIs can cause extreme hypoglycemic episodes and weight gain.
- The newer reversible MAOI, moclobemide, has no known effects on glucose homeostasis or weight.
SNRIs do not appear to disrupt glycemic control and have minimal impact on weight.
- Duloxetine, used for diabetic neuropathy, has little influence on glycemic control.
- Limited data available on venlafaxine, and there's one report of hyperglycemia with desvenlafaxine.
Mirtazapine does not appear to impair glucose tolerance in non-diabetic patients.
- Short-term use showed improvement in HbA1c, but this worsened over a 1-year follow-up.
- Mirtazapine is associated with an increase in BMI in diabetic patients, both short and long-term.
Agomelatine might be effective with some improvement or no worsening of glycemic parameters.
- It also has a minimal effect on body weight.
Reboxetine, trazodone, and vortioxetine have no data available in diabetic patients.
- One study showed a 20% increased risk of type 2 diabetes in those prescribed trazodone.

Sexual Dysfunction & Antidepressants

Sexual dysfunction is common, but reliable data on its prevalence is lacking.
Prevalence rates vary depending on how sexual dysfunction is defined, assessed, and methods used for data collection.
Physical illness, psychiatric illness, substance misuse, and prescribed drug treatment can all cause sexual dysfunction.
People with depression are more likely to be obese, have diabetes, and have cardiovascular disease, making them more prone to sexual dysfunction independent of depression itself.
Before prescribing antidepressants, baseline sexual functioning should be determined using questionnaires or rating scales, like the Arizona Sexual Experience Scale.
Direct questioning is more effective than relying on spontaneous patient reporting for sexual dysfunction.
Complaints of sexual dysfunction may indicate progression or inadequate treatment of underlying medical or psychiatric conditions.
It may also be a result of drug treatment, and intervention can improve quality of life.

Effects of Depression

Both depression and antidepressants can cause disorders of desire, arousal, and orgasm.
The precise nature of the sexual dysfunction can help determine whether depression or antidepressant treatment is the more likely cause.
40-50% of people with depression report diminished libido and problems with sexual arousal before diagnosis, but only 15-20% experience orgasm problems before taking antidepressants.
Loss of libido appears to correlate with depression severity.
While many patients experience treatment-emergent sexual dysfunction on antidepressants, others may see improvements in sexual desire and satisfaction due to reduced depressive symptoms.
Improvements are more common in those who respond to antidepressant treatment.
In the STAR*D study, sexual dysfunction was problematic in 21% of patients whose depression remitted with citalopram treatment compared to 61% of those whose depression did not remit.

Effects of Antidepressant Drugs

Antidepressants can cause sedation, hormonal changes, disturbance of cholinergic/adrenergic balance, peripheral alpha-adrenergic agonism, inhibition of nitric oxide, and increased serotonin neurotransmission, all of which can lead to sexual dysfunction.
Sexual dysfunction has been reported as a side effect of all antidepressants, but rates vary.
Individual susceptibility to sexual dysfunction also varies and may have a genetic component.
Sexual dysfunction with antidepressants is likely to be dose-dependent and is generally considered fully reversible.
However, long-lasting sexual dysfunction has been reported even after discontinuation of SSRIs/SNRIs, known as "post-SSRI sexual dysfunction" (PSSD).
The prevalence and pathophysiology of PSSD remain uncertain.
Not all sexual side effects of antidepressants are undesirable: serotonergic antidepressants, including clomipramine, are effective in treating premature ejaculation and may be beneficial for paraphilias.
The short-acting SSRI dapoxetine is an effective treatment for premature ejaculation and is licensed for this indication in many countries.
A systematic review of randomized controlled trials with trazodone showed benefit in reducing "psychogenic erectile dysfunction."

Management of Antidepressant-Induced Sexual Dysfunction

Careful selection of the antidepressant drug can minimize sexual side effects.
Assessment of sexual side effects in clinical trials is often inadequate, relying on spontaneous reports rather than validated questionnaires and lacking positive controls.
Individual assessment and management strategies are recommended, as there is no single "ideal" approach.
Common management strategies include:
- Switching to a different antidepressant with a lower likelihood of sexual side effects.
- Reducing the dose of the current antidepressant.
- Adding medications specifically for sexual dysfunction, such as sildenafil or tadalafil.
- Lifestyle modifications, such as exercise and stress management.
- Psychotherapy to address psychological factors contributing to sexual dysfunction.

### Antidepressants and Sexual Dysfunction

The impact of antidepressants on sexual response varies, with some antidepressants having significantly lower rates of sexual dysfunction (SD) compared to others.
SSRIs are generally associated with higher rates of SD, affecting sexual desire, arousal, and orgasm.
Bupropion has demonstrated low rates of SD, often comparable to placebo.
Mirtazapine causes less SD than SSRIs.
Moclobemide consistently shows a low risk of SD.
Agomelatine may have rates of SD similar to placebo.
MAOIs have limited evidence, but reported SD ranges from 20% to 42%.
Duloxetine has a rate of SD similar to some SSRIs and venlafaxine.
Levormilnacipran has limited comparative studies, making its SD frequency uncertain.
Reboxetine is suspected to cause less SD than SSRIs/SNRIs, but its efficacy is questioned.
Trazodone has low reports of SD overall, though case studies mention priapism.

Impact on specific sexual response

Sexual desire: SSRIs, MAOIs, and Duloxetine are associated with decreased sexual desire, while Bupropion, Moclobemide, Agomelatine, and Reboxetine show less impact.
Sexual arousal: SSRIs, MAOIs, and Duloxetine are associated with decreased arousal. Bupropion and Trazodone are notable for having a positive or neutral effect.
Orgasm: SSRIs, MAOIs, and Duloxetine are associated with decreased orgasm. Bupropion, Moclobemide, Agomelatine, and Reboxetine have less impact or are neutral.

Impact of Antidepressants on Sexual Function

Tricyclic antidepressants (TCAs) are commonly associated with decreased sexual desire, arousal, and orgasm. Clomipramine, amitriptyline, and imipramine are particularly likely to cause anorgasmia, while desipramine and nortriptyline are less likely.
Venlafaxine is frequently linked to sexual dysfunction, including decreased sexual drive, arousal, and orgasm. However, isolated reports suggest increased libido, orgasm, and spontaneous erections in some individuals.
Vilazodone may have lower rates of sexual dysfunction compared to citalopram and similar rates to placebo according to randomized controlled trials. However, its effectiveness in improving sexual function compared to other antidepressants is uncertain.
Vortioxetine's impact on sexual function is unclear. While studies suggest similar rates of sexual dysfunction to placebo at lower doses (10mg/day or less), its effectiveness compared to other antidepressants is not well-established.

Management of Sexual Adverse Effects

Rule out other possible causes: Depression can impair sexual functioning.
- Compare antidepressant use with the patient's pre-treatment sexual functioning, not before the onset of depression.
- Other factors may contribute, including alcohol/substance misuse, diabetes, atherosclerosis, cardiac disease, and central and peripheral nervous system conditions.
- Other medications may contribute, including both non-psychotropics (e.g., diuretics, beta-blockers) and other psychotropics.
Switch to lower risk antidepressant:
- Lower risk antidepressants include agomelatine, bupropion, mirtazapine, vilazodone, vortioxetine and moclobemide.
- Agomelatine, bupropion and vortioxetine have the best evidence supporting a more favorable sexual side effect profile.
Non-pharmacological treatment strategies:
- Waiting for spontaneous remission:
  - Widely used but least effective method.
  - May occur in a small number of people (5-10%) but can take up to 4-6 months.
  - Impractical for many patients, might be considered in milder cases.
- Dose reduction:
  - Can be considered in patients who have achieved full remission on an antidepressant.
- Drug holidays:
  - Intermittently missing one or two doses prior to planned sexual activity may possibly help but risks discontinuation symptoms.
  - Not an effective strategy with fluoxetine due to its long half-life.
  - Lowering doses to a half for two consecutive days prior to sexual activity could be another possible strategy.

Pharmacological Treatments for Antidepressant-Induced Sexual Dysfunction

Phosphodiesterase inhibitors: Sildenafil and tadalafil can improve sexual functioning in men with antidepressant-related erectile dysfunction. Limited evidence exists for women, but one RCT showed benefits.
Bupropion: May be helpful for women, particularly at higher doses (300mg/day). Lower doses appear ineffective. A positive RCT in men was later retracted.
Mirtazapine: Evidence suggests some benefit for antidepressant-induced sexual dysfunction, but a mixed bag. Some open studies show positive results while one RCT reported negative findings.
Transdermal Testosterone: RCTs indicate its potential effectiveness in women with SSRI/SNRI-induced loss of libido and men taking serotonergic antidepressants with low or low-normal testosterone levels.
Other Agents: Numerous agents have been investigated; however, evidence for their effectiveness is limited or nonexistent.
- Buspirone: Effective in one study for citalopram or paroxetine-induced sexual dysfunction but ineffective in another study with fluoxetine.
- Cyproheptadine: Successfully used in case reports for SSRI-induced sexual dysfunction in men and anorgasmia in women.
- Loratadine: Effective in a small open study for men with SSRI-induced erectile dysfunction.
- Amantadine: Effective in earlier studies for SSRI-induced sexual dysfunction, but recent results have been negative.
- Yohimbine: May be more effective for medication-induced sexual dysfunction. Improvements were reported by patients in two small studies, though results were nonsignificant.
- Bethanechol: Seems to assist with TCA-induced sexual dysfunction when taken before sexual activity.
- Granisetron: Evaluated, but existing data is inconclusive.
- Flibanserin and Bremelanotide: FDA-approved for HSDD in premenopausal women, but lack data supporting their use for antidepressant-induced sexual dysfunction.

Augmenting Agents for Treatment-Resistant Depression

Some drugs used as adjuncts for treatment-resistant depression may improve sexual functioning in secondary analyses.
- Aripiprazole: Improved sexual functioning and desire, but solely in women.
- Brexpiprazole: Associated with modest improvements in one analysis.
- Pimavanserin: Improved sexual functioning when used as an add-on treatment to SSRIs/SNRIs, based on one analysis.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Depression -Maudsley

Choose a study mode

Podcast

Questions and Answers

SSRIs are solely responsible for causing sexual dysfunction.

TCAs are known to cause hypertension as a side effect.

MAOIs can potentially lead to hypertensive crisis when consumed with tyramine-rich foods.

Short half-life antidepressants are less likely to cause discontinuation symptoms than those with longer half-lives.

Fluvoxamine is a potent inhibitor of CYP2D6 and can affect theophylline serum levels.

All antidepressant drugs have the potential to cause drug interactions.

Antidepressants are always the first-line treatment for all types of depression.

The treatment of moderate to severe depression includes the recommendation of a generic SSRI.

Withdrawal from antidepressants should be done suddenly to avoid any negative effects.

The use of electroconvulsive therapy (ECT) is only supported in mild cases of depression.

Patients should be informed about the potential withdrawal effects when prescribed antidepressants.

Psychological treatments can serve as a first-line alternative to antidepressants in severe depression.

For treatment-resistant depression, strategies may include the addition of lithium or an antipsychotic.

Patients with two prior episodes of depression should receive treatment for a minimum of one year.

The new NICE Guidelines for depression treatment are expected to be published in 2021/2022.

All antidepressants show a pattern of response where the rate of improvement is highest during weeks 4-6.

Approximately 30% of patients with moderate-severe depression will respond to a placebo treatment.

Antidepressants are only recommended for patients with severe major depressive disorder.

SSRIs are generally considered less tolerable compared to older tricyclic antidepressants (TCAs).

Only 9% of comparisons in studies showed antidepressants separate from placebo when using total Hamilton Depression Rating Scale scores.

A number needed to treat (NNT) of 5 indicates that for every 5 patients treated with an antidepressant, 1 will benefit compared to those receiving a placebo.

Antidepressants typically take effect within the first week of treatment as seen in larger trials.

Dual re-uptake inhibitors such as venlafaxine are tolerated better than SSRIs.

The use of 'depressed mood' alone as an efficacy measure showed better results in drug comparisons than using total depression scales.

A flexible approach is usually required to find the right drug for each patient due to marked inter-individual variation in tolerability.

Antidepressants should typically be continued for 6-9 months after a single episode of depression.

There is a consensus that long-term treatment with antidepressants is beneficial for all patients.

Antidepressants are not effective in treating anxiety spectrum disorders.

The majority of patients respond well to the first antidepressant prescribed.

Young people have the lowest risk associated with the use of antidepressants.

Treatment-emergent suicidal ideation can occur with any antidepressant treatment.

There is clear and conclusive evidence regarding the optimal duration of treatment for adjunct regimens.

Fluoxetine and paroxetine can both lead to increased health risks due to their effects on CYP2D6.

All types of antidepressants have been implicated in increased suicidal thoughts and behaviors in young adults.

Switching from one antidepressant to another does not influence the risk of suicidal behaviors in patients aged 75 and over.

Electrolyte disturbances from diuretics can reduce the cardiotoxic effects of tricyclic antidepressants (TCAs).

Both the initiation and cessation of antidepressants are associated with increased suicide and self-harm rates.

Tamoxifen is an example of a pro-drug that may experience treatment failure due to the interactions with certain antidepressants.

Antidepressants do not require monitoring for potential drug interactions when switching between them.

The cardiotoxicity of TCAs increases when combined with electrolyte-altering medications.

What is the recommended daily dose of Sertraline?

The recommended minimum effective dose of Agomelatine is 50mg/day.

What is the minimum effective dose of Mirtazapine?

The recommended dose of Fluoxetine is __________ mg/day.

Match the following antidepressants with their respective recommended doses:

Which of the following is suggested as the first-choice medication for depression?

Monitoring a patient's response to antidepressant treatment should occur weekly for the first 1-2 weeks.

What is the importance of involving the patient in the discussion about drug choice?

If a patient experiences no effect or poor tolerance from the initial antidepressant, the next step is to switch to a __________ antidepressant.

Match the following antidepressants with their alternative options:

What should be assessed after initiating antidepressant treatment?

Antidepressants should be maintained for at least 6-9 months after a single episode of depression.

What are the suggested alternative treatment options if initial antidepressants are ineffective?

Patients should be informed about the potential __________ effects when prescribed antidepressants.

How long should a patient be monitored if they have not responded to the increased dose of a new antidepressant?

Which of the following is considered the best scale to measure severity and change in depression?

SSRI medications are generally not recommended for depression treatment in patients needing sedation.

What percentage of patients who do not show improvement at two weeks are likely to eventually respond to treatment?

If a patient cannot tolerate one SSRI, they may still tolerate another ______________.

Match the following antidepressants with their respective properties:

Which option represents a better-supported choice for treatment-resistant depression?

Switching within a drug class is shown to be ineffective for some patients.

What are the two neurotransmitters that dual-action drugs primarily affect?

Which treatment is suggested to be switched after treatment failure?

Increasing the dose of SSRIs generally leads to significant improvements in depression.

What is a good predictor of overall non-response in antidepressant treatment?

Patients should switch treatments if there is no improvement after ______ weeks.

Match the following medications with their known characteristics:

Which option reflects common misconceptions regarding treatment-resistant depression?

The STAR*D program confirmed that treatment-resistant depression requires a rigid approach.

What percentage of subjects achieved remission after the first stage of the STAR*D study?

The combination of mirtazapine and venlafaxine was found to be _________ and has a safety profile.

Which outcome is mainly assessed in the STAR*D program?

What is a common side effect of adding aripiprazole to an antidepressant?

Lithium is known to be well tolerated at higher plasma levels.

What does combining olanzapine and fluoxetine aim to address in treatment-resistant depression?